Cerebrospinal fluid eosinophilia and sterile shunt malfunction.

PubMed

Traynelis, V C; Powell, R G; Koss, W; Schochet, S S; Kaufman, H H

1988-11-01

Cerebrospinal fluid (CSF) eosinophilia is a rare finding most often associated with central nervous system inflammatory processes, including parasitic, bacterial, and mycotic infections. It has also been seen as an allergic phenomenon. We present two cases of CSF eosinophilia occurring concurrently with sterile shunt malfunction. We speculate that CSF eosinophilia in our patients might have resulted from an allergic response to a foreign material such as suture, surgical glove powder, hair, cotton fibers, antibiotics, or silicone rubber. The incidence of sterile CSF eosinophilia after shunting is not known. Information concerning the role of eosinophilia in the development of shunt malfunctions is also lacking. An increased awareness of this possibility and further investigation are warranted.

Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus

PubMed Central

2014-01-01

Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD). Methods: We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings. Results: In NPH, β-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently. Conclusions: In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD. PMID:25332445

Concurrent Alzheimer's pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes.

PubMed

Pomeraniec, I Jonathan; Bond, Aaron E; Lopes, M Beatriz; Jane, John A

2016-02-01

Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer's disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided. The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups. From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer's pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer's pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136). A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evidence of AD pathology on repeat biopsy, demonstrating the progressive nature of the disease.

Quality measures for the management of hydrocephalus: concepts, simulations, and preliminary field-testing.

PubMed

Barton, Spencer E; Campbell, Jeffrey W; Piatt, Joseph H

2013-04-01

The authors define and examine the properties of 2 new, practice-based quality measures for the management of hydrocephalus. The Surgical Activity Rate (SAR) is defined as the number of definitive operations for the treatment of hydrocephalus performed in a neurosurgical practice over the course of a year, divided by the number of patients with hydrocephalus seen in follow-up during that year. The Revision Quotient (RQ) is defined as the number of definitive revision operations performed in a neurosurgical practice in the course of a year, divided by the number of definitive initial operations during that year for patients with newly diagnosed hydrocephalus. Using published actuarial shunt survival data, the authors conducted Monte Carlo simulations of a pediatric neurosurgical practice to illustrate the properties and interpretations of the SAR and RQ. They used data from the Kids' Inpatient Database (KID) for 2009 to calculate RQs for hospitals accounting for more than 10 admissions coded for initial CSF shunt insertions. During the initial growth phase of a simulated neurosurgical practice, the SAR approached its steady-state value much earlier than the RQ. Both measures were sensitive to doubling or halving of monthly failure rates. In the 2009 KID, 117 hospitals reported more than 10 initial shunt insertions. The weighted mean (± standard deviation) RQ for these hospitals was 1.79 ± 0.69. Among hospitals performing 50 or more initial shunt insertions, the RQ ranged between 0.71 and 3.65. The SAR and RQ have attractive qualitative features as practice-based quality measures. The RQ, at least, exhibits clinically meaningful interhospital variation as applied to CSF shunt surgery. The SAR and RQ merit prospective field-testing as measures of quality in the management of childhood hydrocephalus.

A new shunt for obstructive hydrocephalus: ventricle-Sylvian fissure shunt A preliminary report.

PubMed

Patkar, Sushil

2017-06-01

Cerbrospinal fluid (CSF) pathway studies have revealed that after egressing from the fourth ventricle reaches the basal supra sellar cistern and ultimately the sylvian cisterns from where the CSF travels over the cerebral convexity subarachnoid space to reach the superior saggital sinus and enters the blood stream. Diverting CSF from the lateral ventricle with a shunt catheter to the sylvian cistern can be an option to treat obstructive hydrocephalus. 2 patients underwent this procedure of diverting CSF from the lateral ventricle with a shunt catheter (Chabbra, India) to the sylvian cistern successfully and had immediate relief of symptoms of raised intracranial pressure. Additional 4 patients had relief for 3mths to 6 mths and are under follow up. Though preliminary results seem logical and promising, more cases and longer follow-up is required to consider this shunt operation as an option in treatment of obstructive hydrocephalus.

[Contribution of phase-contrast MRI to the management of patients with normal pressure hydrocephalus: Can it predict response to shunting?].

PubMed

Mouton Paradot, Gaëlle; Baledent, Olivier; Sallioux, Guillaume; Lehmann, Pierre; Gondry-Jouet, Catherine; Le Gars, Daniel

2010-02-01

The diagnosis and management of patients with idiopathic normal-pressure hydrocephalus (NPH) remain somewhat controversial and there is no clear guideline for assessing the post-shunt outcome. The objective of this study was to investigate whether cerebrospinal fluid (CSF) flow dynamics is linked to post-shunt improvement. Fourteen NPH patients (nine males and five females; mean age, 68 years) investigated by magnetic resonance imaging (MRI) before surgical diversion of CSF were retrospectively reviewed. Phase-contrast sequences were added to the morphological clinical protocol for quantification of CSF oscillations, which were recorded at the level of the cerebral aqueduct and the C2 and C3 subarachnoid spaces (SAS). The phase-contrast images were analysed with custom-designed dedicated flow segmentation software. The oscillations measured in this hydrocephalus population were compared to a previously studied healthy population. A difference of at least two standard deviations was used to define a hyperdynamic or hypodynamic state of CSF flow. The cervical CSF flow of the hydrocephalus patients was not significantly different from those of the volunteer population. Of the 14 hydrocephalus patients, 12 had a good response to the shunt. Of these, 10 presented an increased ventricular CSF flow, one a low ventricular CSF flow, and the last one had a normal ventricular CSF flow. Phase-contrast MRI can help develop guidelines for surgical management of NPH. The shunt responders appear to be the patients with hyperdynamic ventricular CSF flow and normal cervical CSF flow. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Cerebrospinal Fluid Lumbar Tapping Utilization for Suspected Ventriculoperitoneal Shunt Under-Drainage Malfunctions

PubMed Central

Lee, Jong-Beom; Ahn, Ho-Young; Lee, Hong-Jae; Yang, Ji-Ho; Yi, Jin-Seok; Lee, Il-Woo

2017-01-01

Objective The diagnosis of shunt malfunction can be challenging since neuroimaging results are not always correlated with clinical outcomes. The purpose of this study was to evaluate the efficacy of a simple, minimally invasive cerebrospinal fluid (CSF) lumbar tapping test that predicts shunt under-drainage in hydrocephalus patients. Methods We retrospectively reviewed the clinical and radiological features of 48 patients who underwent routine CSF lumbar tapping after ventriculoperitoneal shunt (VPS) operation using a programmable shunting device. We compared shunt valve opening pressure and CSF lumbar tapping pressure to check under-drainage. Results The mean pressure difference between valve opening pressure and CSF lumbar tapping pressure of all patients were 2.21±24.57 mmH2O. The frequency of CSF lumbar tapping was 2.06±1.26 times. Eighty five times lumbar tapping of 41 patients showed that their VPS function was normal which was consistent with clinical improvement and decreased ventricle size on computed tomography scan. The mean pressure difference in these patients was −3.69±19.20 mmH2O. The mean frequency of CSF lumbar tapping was 2.07±1.25 times. Fourteen cases of 10 patients revealed suspected VPS malfunction which were consistent with radiological results and clinical symptoms, defined as changes in ventricle size and no clinical improvement. The mean pressure difference was 38.07±23.58 mmH2O. The mean frequency of CSF lumbar tapping was 1.44±1.01 times. Pressure difference greater than 35 mmH2O was shown in 2.35% of the normal VPS function group (2 of 85) whereas it was shown in 64.29% of the suspected VPS malfunction group (9 of 14). The difference was statistically significant (p=0.000001). Among 10 patients with under-drainage, 5 patients underwent shunt revision. The causes of the shunt malfunction included 3 cases of proximal occlusion and 2 cases of distal obstruction and valve malfunction. Conclusion Under-drainage of CSF should be suspected if CSF lumbar tapping pressure is 35 mmH2O higher than the valve opening pressure and shunt malfunction evaluation or adjustment of the valve opening pressure should be made. PMID:28061484

Flow void of cerebrospinal fluid in idiopathic normal pressure hydrocephalus of the elderly: can it predict outcome after shunting?

PubMed

Krauss, J K; Regel, J P; Vach, W; Jüngling, F D; Droste, D W; Wakhloo, A K

1997-01-01

We investigate the predictive value of cerebrospinal fluid (CSF) flow void on outcome after shunting in a prospective series of patients with idiopathic normal pressure hydrocephalus (NPH). The degree and extension of CSF flow void were examined on T2-weighted magnetic resonance imaging scans of 37 elderly patients with idiopathic NPH who underwent subsequent shunting. The degree of flow void was assessed in comparison with the signal of large cerebral arteries. The extension was evaluated via the calculation of sum scores for the occurrence of flow void in different locations of the ventricular system. Those parameters were not considered in the decision to perform shunting. CSF flow void in the aqueduct and the adjacent third and fourth ventricles of the 37 patients with idiopathic NPH was compared with that of 37 age-matched control patients. CSF flow void scores in patients with idiopathic NPH were investigated for correlations between postoperative outcome scores and ventricular width indices. No difference was found between the occurrence of aqueductal CSF flow void in patients with idiopathic NPH and the control group. A significant difference, however, was noted for the extension of the CSF flow void, which was greater in the NPH group. Postoperative improvement was found in 33 of 37 patients with idiopathic NPH at a mean follow-up of 15.6 months. Only small, statistically not significant correlations were found between CSF flow void and postoperative outcome. Flow void sum scores, however, correlated significantly with ventricular width indices. The degree and extension of CSF flow void on T2-weighted magnetic resonance imaging scans have little predictive value for outcome after shunting in patients with idiopathic NPH. The greater extension of the CSF flow void in patients with NPH is most likely related to increased ventricular width. It is not useful to consider CSF flow void findings on conventional magnetic resonance imaging scans in making the decision to offer shunting in patients with idiopathic NPH.

Cerebrospinal fluid dynamics study in communicating hydrocephalus.

PubMed

Ramesh, Vengalathur Ganesan; Narasimhan, Vidhya; Balasubramanian, Chandramouli

2017-01-01

Communicating hydrocephalus often poses a challenge in diagnosis and management decisions. The objective of this study is to measure the opening pressure (P o ), pressure volume index (PVI), and cerebrospinal fluid outflow resistance (R out ), in patients with communicating hydrocephalus using bolus lumbar injection method and to evaluate its diagnostic and prognostic value. The study was conducted in 50 patients with communicating hydrocephalus, including normal pressure hydrocephalus (NPH) (19), post-meningitic hydrocephalus (23) and post-traumatic hydrocephalus (8). An improvised bolus lumbar injection method [the Madras Institute of Neurology (MIN) method] was used. In the NPH Group, the CSF dynamics studies correlated well with the clinico-radiological classification. The prediction of shunt responsiveness by CSF dynamics studies correlated with good outcome in 87.5%. In the post-meningitic hydrocephalus group, the value of CSF dynamics studies in predicting patients needing shunt was 89.5%. The CSF dynamics studies detected patients who needed shunt earlier than clinical or radiological indications. In the post-traumatic hydrocephalus group, 62.5% of patients improved with the treatment based on CSF dynamics studies. The improvised bolus lumbar injection method (MIN method) is a very simple test with fairly reliable and reproducible results. Study of CSF dynamics is a valuable tool in communicating hydrocephalus for confirmation of diagnosis and predicting shunt responsiveness. This is the first time that the value of CSF dynamics has been studied in patients with post-meningitic hydrocephalus. It was also useful for early selection of cases for shunting and for identifying patients with atrophic ventriculomegaly, thereby avoiding unnecessary shunt.

Cerebrospinal fluid dynamics study in communicating hydrocephalus

PubMed Central

Ramesh, Vengalathur Ganesan; Narasimhan, Vidhya; Balasubramanian, Chandramouli

2017-01-01

Context: Communicating hydrocephalus often poses a challenge in diagnosis and management decisions. Aims: The objective of this study is to measure the opening pressure (Po), pressure volume index (PVI), and cerebrospinal fluid outflow resistance (Rout), in patients with communicating hydrocephalus using bolus lumbar injection method and to evaluate its diagnostic and prognostic value. Materials and Methods: The study was conducted in 50 patients with communicating hydrocephalus, including normal pressure hydrocephalus (NPH) (19), post-meningitic hydrocephalus (23) and post-traumatic hydrocephalus (8). An improvised bolus lumbar injection method [the Madras Institute of Neurology (MIN) method] was used. Results: In the NPH Group, the CSF dynamics studies correlated well with the clinico-radiological classification. The prediction of shunt responsiveness by CSF dynamics studies correlated with good outcome in 87.5%. In the post-meningitic hydrocephalus group, the value of CSF dynamics studies in predicting patients needing shunt was 89.5%. The CSF dynamics studies detected patients who needed shunt earlier than clinical or radiological indications. In the post-traumatic hydrocephalus group, 62.5% of patients improved with the treatment based on CSF dynamics studies. Conclusions: The improvised bolus lumbar injection method (MIN method) is a very simple test with fairly reliable and reproducible results. Study of CSF dynamics is a valuable tool in communicating hydrocephalus for confirmation of diagnosis and predicting shunt responsiveness. This is the first time that the value of CSF dynamics has been studied in patients with post-meningitic hydrocephalus. It was also useful for early selection of cases for shunting and for identifying patients with atrophic ventriculomegaly, thereby avoiding unnecessary shunt. PMID:28484522

Correlation between lumbo-ventricular perfusion and MRI-CSF flow studies in idiopathic normal pressure hydrocephalus.

PubMed

Hakim, R; Black, P M

1998-01-01

After the initial description of normal pressure hydrocephalus (NPH) and its clinical triad, there has been a continuous interest from clinicians and researchers to set different diagnostic criteria that would make the selection of candidates for shunt surgery easier and more precise. A preliminary group of 12 patients was given a diagnosis of idiopathic normal pressure hydrocephalus by clinical and radiologic criteria. Each patient underwent two different tests: a magnetic resonance imaging-cerebrospinal fluid (MRI-CSF) flow study and a lumbo-ventricular perfusion test. The purpose was to compare the correlation of the results obtained with these tests and the clinical results obtained after CSF diversion. Eleven patients were given shunts and one was managed with lumbar punctures. One year after treatment, 10 of the 12 patients had improved with good results. The MRI-CSF flow studies were reliable in six patients; there were five false negatives and one false positive. The lumbo-ventricular perfusion test showed reliability in nine patients; there were two false negatives and one false positive. In only three patients were the results of both of these tests in accordance with the outcome. Even though there are few patients in this study so far, the data suggests that at the present time the most predictive guides for the diagnosis of NPH and its outcome after shunting are the clinical criteria and the radiological findings in computed tomography (CT) and/or MRI rather than lumbo-ventricular perfusion and CSF flow studies.

Cerebrospinal fluid (CSF) shunting and ventriculocisternostomy (ETV) in 400 pediatric patients. Shifts in understanding, diagnostics, case-mix, and surgical management during half a century.

PubMed

Paulsen, A Henriette; Due-Tønnessen, Bernt J; Lundar, Tryggve; Lindegaard, Karl-Fredrik

2017-02-01

To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009-2013. This represents our current practice. Our previously reported cohorts of shunted children 1967-1970 (n = 128) and 1985-1988 (n = 138) served as backgrounds for comparison. In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009-2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis was a small but distinctive group in all cohorts with 5, 6 and 3 % respectively. The case-mix in pediatric patients treated with permanent CSF diversion has changed over the last half-century. With the higher proportion of children with CNS tumor patients and inclusion of the IIH children, the median age at initial surgery has shifted substantially from 3.2 to 14 months. Between the 1960s and the current cohort, 2 years of all-cause mortality fell from 24 to 8 %. Prolonged asymptomatic periods, extending 15 years, were relatively common. Nevertheless, 18 patients experienced shunt failure more than 15 years after last revision, and first-time shunt failure has been observed 29 years after initial treatment. This underscores the importance of life-long follow-up.

Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

PubMed

Santos, Marcelo Volpon; Garcia, Camila Araujo Bernardino; Jardini, Evelise Oliveira; Romeiro, Thais Helena; da Silva Lopes, Luiza; Machado, Hélio Rubens; de Oliveira, Ricardo Santos

2016-08-01

Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.

Diamox((R)) challenge test to decide indications for cerebrospinal fluid shunting in normal pressure hydrocephalus.

PubMed

Miyake, H; Ohta, T; Kajimoto, Y; Deguchi, J

1999-01-01

The indications for cerebrospinal fluid (CSF) shunting in patients with normal pressure hydrocephalus (NPH) have not been established. Establishment of clear-cut indications for this procedure is essential to ensure cost-effective, and safe treatment. We report the usefulness of the Diamox((R)) challenge test in evaluating indications for CSF shunting in patients with NPH. Pre- and post-operative responses in cerebral blood flow (CBF) and intracranial pressure (ICP) to intravenous administration of Diamox((R)) 1000mg (Diamox((R)) administration) were analysed in 41 patients with NPH who were treated by ventriculoperitoneal (VP) shunt with a programmable valve and an on-off valve. The preoperative response of ICP to Diamox((R)) administration was more than 10 mmHg in most patients in whom the shunt was effective (shunt effective group), however, it was less than 10 mmHg in most patients in whom the shunt was ineffective (shunt non-effective group). Furthermore, the postoperative response of ICP to Diamox((R)) administration decreased to less than 10 mmHg in most patients in the shunt effective group. The increases in CBF in response to Diamox((R)) administration were similar in the two groups both before and after placement of the VP shunt. Patients in whom ICP increased by more than 10 mmHg in response to Diamox((R)) administration were regarded to have poor CSF circulation and to thus be candidates for CSF shunting. The Diamox((R)) challenge test is a simple, safe procedure, useful in evaluating the response to treatment.

Management of complicated shunt infections: a clinical report.

PubMed

James, Hector E; Bradley, John S

2008-03-01

The authors present their experience with a protocol for the treatment of patients with complicated shunt infections. Complicated shunt infections are defined for the purpose of this protocol as multiple compartment hydrocephalus, multiple organism shunt infection, severe peritonitis, or infections in other sites of the body. The initial treatment protocol for these patients was 3 weeks of intravenous antibiotic therapy and 2 weeks of twice daily intraventricular/intrashunt antibiotic therapy. Cerebrospinal fluid (CSF) cultures were monitored during therapy and obtained again 48 hours after completion. The shunt was completely replaced. Additionally, follow-up cultures were obtained in all patients 3-6 months after therapy was completed. A cure of the infection was achieved in all patients as defined by negative cultures obtained at completion of antibiotic therapy and in follow-up studies. The follow-up period was 2-11 years (mean 4.4 +/- 2.5 years). The treatment protocol was modified in the patients treated after 1991, and 18 patients were treated with this modified treatment regime. In these patients, intraventricular antibiotics were administered only once daily for 14 days, and the CSF was cultured 24 hours after antibiotic therapy had been stopped instead of after 48 hours. The results were similar to those obtained with the initial protocol. Based on their prospective nonrandomized series, the authors believe that patients with complicated shunt infections can be successfully treated with 2 weeks of intraventricular antibiotic therapy administered once daily, concurrent with 3 weeks of intravenous antibiotic therapy. This protocol reduces length of treatment and hospital stay, and avoids recurrence of infection.

The importance of the cortical subarachnoid space in understanding hydrocephalus.

PubMed

Rekate, Harold L; Nadkarni, Trimurti D; Wallace, Donna

2008-07-01

In this paper the authors define the role of the cortical subarachnoid space (CSAS) in poorly understood forms of hydrocephalus to cerebrospinal fluid (CSF) dynamics to improve understanding of the importance of the CSAS and its role in selecting patients for endoscopic third ventriculostomy (ETV). The secondary purpose of this work was to define testable hypotheses to explain enigmatic disorders of CSF dynamics and to suggest how these concepts could be tested. The magnitude of the contribution of the CSAS is explored using the solid geometry of concentric spheres. With this starting point, clinical conditions in which CSF dynamics are not easily understood are explored regarding the potential role of the CSAS. Overall, problems of CSF dynamics are easily understood. Insights may be gained when the results of a pathological process or its treatment vary from what has been expected. Acute changes in ventricular volume at the time that hydrocephalus develops, the failure of shunts, and the changes in ventricular volume with shunt repair may occur very rapidly. Changes in the volume of water in the brain, especially in the brain substance itself, are unlikely to occur at this rapid rate and may be interpreted as a simple redistribution of the CSF between the ventricle and CSAS with no initial change in the actual volume of brain parenchyma. Problems such as pseudotumor cerebri, shunt failure with nonresponsive ventricles, and negative-pressure hydrocephalus can be explained by assessing the ability of ventricular CSF to flow to the CSAS and the ability of this fluid to exit this compartment. Ventricular enlargement at the time of shunt failure implies a failure of flow between the ventricles and CSAS, implying that all patients who show this phenomenon are potential candidates for ETV. The important role of the CSAS in the pathophysiology of various forms of hydrocephalus has been largely ignored. Attention to the dynamics of the CSF in this compartment will improve understanding of enigmatic conditions of hydrocephalus and improve selection criteria for treatment paradigms such as ETV. These concepts lead to clearly defined problems that may be solved by the creation of a central database to address these issues.

The predictive value of cerebrospinal fluid tap-test in normal pressure hydrocephalus.

PubMed

Damasceno, B P; Carelli, E F; Honorato, D C; Facure, J J

1997-06-01

Eighteen patients (mean age of 66.5 years) with normal pressure hydrocephalus (NPH) underwent a ventriculo-peritoneal shunt surgery. Prior to operation a cerebrospinal fluid tap-test (CSF-TT) was performed with measurements of gait pattern and psychometric functions (memory, visuo-motor speed and visuo-constructive skills) before and after the removal of 50 ml CSF by lumbar puncture (LP). Fifteen patients improved and 3 were unchanged after surgery. Short duration of disease, gait disturbance preceding mental deterioration, wide temporal horns and small sulci on CT-scan were associated with good outcome after shunting. There was a good correlation between the results of CSF-TT and shunt surgery (chi 2 = 4.11, phi = 0.48, p < 0.05), with gait test showing highest correlation (r = 0.99, p = 0.01). In conclusion, this version of CSF-TT proved to be an effective test to predict improvement after shunting in patients with NPH.

Cerebrospinal fluid rhinorrhea following trans-sphenoidal pituitary macroadenoma surgery: experience from 592 patients.

PubMed

Han, Zong-Li; He, Dong-Sheng; Mao, Zhi-Gang; Wang, Hai-Jun

2008-06-01

To determine the incidence, risk factors, diagnostic procedures, and management of cerebrospinal fluid (CSF) leaks following trans-sphenoidal pituitary macroadenoma surgery. Retrospective analysis of 592 patients. Intra- and post-operative CSF leaks occurred in 14.2 and 4.4% of patients, respectively. Surgical revision, tumor consistency, and tumor margins were independently associated with intra-operative leaks, while the tumor size, consistency, and margins were risk factors of post-operative leaks. The intra-operative leak rate of ACTH adenomas was greater than all other types combined; the incidence of post-operative CSF leaks was highest for FSH adenomas. There were no significant differences among various techniques and we achieved an initial repair success rates of 83.3 and 92.9% for intra- and post-operative CSF leaks, respectively. Of the 26 patients with post-operative CSF leaks, five were complicated by meningitis and four by post-infectious hydrocephalus which required ventriculoperitoneal shunts. CSF leaks have a propensity to occur in cases with fibrous tumors or tumors with indistinct margin and may have some relationship with the tumor type. Endoscopic and microscopic repairs were shown to be effective techniques in managing these types of leaks. Post-infectious hydrocephalus may influence the outcome of the repair and ventriculoperitoneal shunts were necessary in some cases.

Outcome of infants shunted for post-haemorrhagic ventricular dilatation.

PubMed

Hislop, J E; Dubowitz, L M; Kaiser, A M; Singh, M P; Whitelaw, A G

1988-08-01

Between April 1980 and March 1986, 19 infants underwent cerebrospinal fluid (CSF) shunting procedures for post-haemorrhagic ventricular dilatation at the Hammersmith Hospital, London. A total of 58 shunt-related procedures have been performed on these children. The major perioperative complication was seizure activity (eight children). Postoperative complications included infection (12 shunts) and blockage (29 shunts). Prophylactic antibiotics failed to prevent shunt infection. The likelihood of the first shunt failing was significantly reduced by greater weight of the infant and lower CSF protein at surgery. Long-term outcome was poor: three have died and another four are quadriplegic with severe mental retardation. Only four children are developmentally normal. These outcomes cannot be related to the shunt surgery or its complications, but correlate best with pre-operative parenchymal brain-lesions, as shown on ultrasound scans.

Twenty-year outcome in young adults with childhood hydrocephalus: assessment of surgical outcome, work participation, and health-related quality of life.

PubMed

Paulsen, A Henriette; Lundar, Tryggve; Lindegaard, Karl-Fredrik

2010-12-01

Shunting of CSF is one of the most commonly performed operations in the pediatric neurosurgeon's repertoire. The 1st decade after initial shunt insertion has been addressed in several previous reports. The goals of the authors' study, therefore, were to determine 20-year outcomes in young adults with childhood hydrocephalus and to assess their health-related quality of life (HRQOL). Patients younger than 15 years of age, in whom a first-time shunt insertion was performed for hydrocephalus in the calendar years 1985-1988, were included in a retrospective study on surgical morbidity, mortality rates, academic achievement, and/or work participation. Information concerning perceived health and functional status was assessed using the 36-Item Short Form Health Survey (SF-36) and Barthel Index, which were completed by patients still alive by September 1, 2009. Overall, 138 patients participated, no patient being lost to follow-up. For the 20-year period, the overall mortality rate was 21.7%. The mortality rate was not significantly higher in the 1st decade after initial shunt insertion than in the 2nd decade (p = 0.10). Ten percent of the patients surviving still live with their primary shunt in place, whereas 81% required at least one revision, and among these individual the mean number of revisions was 4.2 (median 3, range 0-26). There was a significantly higher revision rate during the 1st decade after initial shunt insertion compared with the 2nd decade (p = 0.027). The majority of patients live lives comparable with those of their peers. At follow-up, 56% were employed in open-market jobs or were still students, 23% had sheltered employment, and 21% were unemployed. The HRQOL was slightly lower in the hydrocephalic cohort than in the normative population. A significant difference was found in 2 of 8 SF-36 domains-Physical Functioning and General Health. During the 20-year follow-up period, 81% of the patients required at least one revision of the CSF shunt. The mortality rate was high: 24 patients died in the 1st decade and 6 died in the 2nd decade after implantation of the initial shunt. In total, 4 deaths (2.9%) were due to shunt failure. Shunt placement to treat childhood hydrocephalus has a substantial effect on social functioning in later life, although perceived health was positively found to be better than expected in young adults with hydrocephalus.

[The role of computerized rheoencephalography in the assessment of normal pressure hydrocephalus. Preliminary report].

PubMed

Traczewski, Wojciech; Moskała, Marek; Szwabowska, Dorota; Gościński, Igor; Krupa, Mariusz; Polak, Jarosław

2005-01-01

It is generally agreed that the positive result of lumbar cerebrospinal fluid (CSF) withdrawal offers a reliable means for selection of patients likely to respond to shunting in normal pressure hydrocephalus (NPH). However the studies of cerebral hemodynamics in NPH are performed Routinely only in few neurosurgical centers. We therefore studied the effect of CSF withdrawal on cerebrovascular autoregulation (CVA) in this condition by means of computerized rheoencephalography [REG]. The study group consisted of 27 patients with presumed posttraumatic NPH. In each patient both the tap test and infusion test were performed. Psychometric tests and rheoencephalographic examinations were made twice: before and after CSF withdrawal. The obvious restoration of the functional state of CVA after CSF withdrawal was considered as a positive result of the tap test. Fourteen patients with a positive tap test and/or with resistance to CSF outflow (Rout) of more than 11 mmHg/ml/min were shunted. The improvement was obtained in 10 of them. Only one patient with a positive tap test did not improve. Our study suggests that restoration of CVA after CSF withdrawal is associated with high likelihood of shunt success, but not vice versa. Evaluation of CVA using REG seems to offer a new diagnostic tool in selecting patients likely to respond to shunting. Further studies are necessary to optimize the amount of CSF withdrawal, the delay between CSF withdrawal and control examinations and methodology of neuropsychological examinations.

Shunting for normal pressure hydrocephalus (NPH).

PubMed

Esmonde, T; Cooke, S

2002-01-01

Since the condition was first described in 1965, the syndrome of normal pressure hydrocephalus (NPH) has conventionally been managed by placement of a cerebrospinal fluid (CSF) shunt. To determine the effectiveness of shunting procedures in promoting stability or improvement in the neurological symptoms and signs of NPH. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 June 2001 using the terms 'shunt*' and 'normal pressure hydrocephalus'. Studies included for analysis were those involving the placement of a CSF shunt for the treatment of NPH as part of a randomized controlled trial. No data matching the selection criteria were found. No randomized controlled trials of shunt placement versus no shunt were found. There is no evidence to indicate whether placement of a shunt is effective in the management of NPH.

FSI simulation of CSF hydrodynamic changes in a large population of non-communicating hydrocephalus patients during treatment process with regard to their clinical symptoms

PubMed Central

2018-01-01

3D fluid-structure interaction modelling was utilized for simulation of 13 normal subjects, 11 non-communicating hydrocephalus (NCH) patients at pre-treatment phase, and 3 patients at five post-treatment phases. Evaluation of ventricles volume and maximum CSF pressure (before shunting) following results validation indicated that these parameters were the most proper hydrodynamic indices and the NCH type doesn’t have any significant effect on changes in two indices. The results confirmed an appropriate correlation between these indices although the correlation decreased slightly after the occurrence of disease. NCH raises the intensity of vortex and pulsatility (2.4 times) of CSF flow while the flow remains laminar. On day 18 after shunting, the CSF pressure decreased 81.0% and all clinical symptoms of patients vanished except for headache. Continuing this investigation during the treatment process showed that maximum CSF pressure is the most sensitive parameter to patients’ clinical symptoms. Maximum CSF pressure has decreased proportional to the level of decrease in clinical symptoms and has returned close to the pressure range in normal subjects faster than other parameters and simultaneous with disappearance of patients’ clinical symptoms (from day 81 after shunting). However, phase lag between flow rate and pressure gradient functions and the degree of CSF pulsatility haven’t returned to normal subjects’ conditions even 981 days after shunting and NCH has also caused a permanent volume change (of 20.1%) in ventricles. Therefore, patients have experienced a new healthy state in new hydrodynamic conditions after shunting and healing. Increase in patients’ intracranial compliance was predicted with a more accurate non-invasive method than previous experimental methods up to more than 981 days after shunting. The changes in hydrodynamic parameters along with clinical reports of patients can help to gain more insight into the pathophysiology of NCH patients. PMID:29708982

A wireless monitoring system for Hydrocephalus shunts.

PubMed

Narayanaswamy, A; Nourani, M; Tamil, L; Bianco, S

2015-08-01

Patients with Hydrocephalus are usually treated by diverting the excess Cerebrospinal Fluid (CSF) to other parts of the body using shunts. More than 40 percentage of shunts implanted fail within the first two years. Obstruction in the shunts is one of the major causes of failure (45 percent) and the detection of obstruction reduces the complexity of the revision surgery. This paper describes a proposed wireless monitoring system for clog detection and flow measurement in shunts. A prototype was built using multiple pressure sensors along the shunt catheters for sensing the location of clog and flow rate. Regular monitoring of flow rates can be used to adjust the valve in the shunt to prevent over drainage or under drainage of CSF. The accuracy of the flow measurement is more than 90 percent.

Impact of Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus on the Amyloid Cascade

PubMed Central

Moriya, Masao; Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Arai, Hajime

2015-01-01

The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-peptide (Aβ), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β) (a surrogate marker for Aβ). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and Aβ38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ≥ 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate) to Aβ38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH. PMID:25821958

Shunt-dependent hydrocephalus: management style among members of the American Society of Pediatric Neurosurgeons.

PubMed

Kraemer, Mark R; Sandoval-Garcia, Carolina; Bragg, Taryn; Iskandar, Bermans J

2017-09-01

OBJECTIVE The authors conducted a survey to evaluate differences in the understanding and management of shunt-dependent hydrocephalus among members of the American Society of Pediatric Neurosurgeons (ASPN). METHODS Surveys were sent to all 204 active ASPN members in September 2014. One hundred thirty responses were received, representing a 64% response rate. Respondents were asked 13 multiple-choice and free-response questions regarding 4 fundamental problems encountered in shunted-hydrocephalus management: shunt malfunction, chronic cerebrospinal fluid (CSF) overdrainage, chronic headaches, and slit ventricle syndrome (SVS). RESULTS Respondents agreed that shunt malfunction occurs most often as the result of ventricular catheter obstruction. Despite contrary evidence in the literature, most respondents (66%) also believed that choroid plexus is the tissue most often found in obstructed proximal catheters. However, free-text responses revealed that the respondents' understanding of the underlying pathophysiology of shunt obstruction was highly variable and included growth, migration, or adherence of choroid plexus, CSF debris, catheter position, inflammatory processes, and CSF overdrainage. Most respondents considered chronic CSF overdrainage to be a rare complication of shunting in their practice and reported wide variation in treatment protocols. Moreover, despite a lack of evidence in the literature, most respondents attributed chronic headaches in shunt patients to medical reasons (for example, migraines, tension). Accordingly, most respondents managed headaches with reassurance and/or referral to pain clinics. Lastly, there were variable opinions on the etiology of slit ventricle syndrome (SVS), which included early shunting, chronic overdrainage, and/or loss of brain compliance. Beyond shunt revision, respondents reported divergent SVS treatment preferences. CONCLUSIONS The survey shows that there is wide variability in the understanding and management of shunt-dependent hydrocephalus and its complications. Such discrepancies appear to be derived partly from inconsistent familiarity with existing literature but especially from a paucity of high-quality publications.

Laparoscopic treatment of abdominal complications following ventriculoperitoneal shunt

PubMed Central

Grigorean, VT; Onose, G; Popescu, M; Strambu, V; Sandu, AM

2009-01-01

The aim of this study is the evaluation of laparoscopic treatment in abdominal complications following ventriculoperitoneal (VP) shunt. Methods: We report a retrospective study including 17 patients with abdominal complications secondary to VP shunt for hydrocephalus, laparoscopically treated in our department, between 2000 and 2007. Results: Patients' age ranged from 1 to 72 years old (mean age 25.8 years old). Male: female ratio was 1.4. Abdominal complications encountered were: shunt disconnection with intraperitoneal distal catheter migration 47.05% (8/17), infections 23.52% (4/17) such as abscesses and peritonitis, pseudocysts 11.76% (2/17), CSF ascites 5.88% (1/17), inguinal hernia 5.88% (1/17), and shunt malfunction due to excessive length of intraperitoneal tube 5.88% (1/17). Free–disease interval varies from 1 day to 21 years, depending on the type of complication, short in peritoneal irritation syndrome and abscesses (days) and long in ascites, pseudocysts(months– years). Laparoscopic treatment was: extraction of the foreign body in shunt disconnection with intraperitoneal distal catheter migration, evacuation, debridement, lavage and drainage for pseudocysts, abscess and peritonitis, shortening of the tube in shunt malfunction due to excessive length of intraperitoneal tube a nd hernioraphy. One diagnostic laparoscopy was performed in a peritoneal irritation syndrome, which found only CSF ascites. There were no conversions to open surgery. The overall mortality was of 5.88% and postoperative morbidity was of 11.76%. In 7 patients operated for abscesses, peritonitis, pseudocysts, and CSF ascites the shunting system was converted in to a ventriculocardiac shunt. Conclusions: Abdominal complication following VP shunt can be successfully performed laparoscopically. Abdominal surgery required, in selected cases, the repositioning of the distal catheter, frequently as a ventriculocardiac shunt. There are abdominal complications with no indication of surgery, like peritoneal irritation syndrome and CSF ascites. Free– disease interval varies from days (peritoneal irritation syndrome, abscesses) to month–years (pseudocyst, ascites), according to type of complication. PMID:20108757

The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus

PubMed Central

Walchenbach, R; Geiger, E; Thomeer, R; Vanneste, J

2002-01-01

Objective: It has been reported that temporary external lumbar CSF drainage (ELD) is a very accurate test for predicting the outcome after ventricular shunting in patients with normal pressure hydrocephalus (NPH). However, only a limited number of patients have been studied for assessing the predictive accuracy of ELD. Therefore, the value of ELD in predicting the outcome after a ventriculoperitoneal shunt in patients with presumed NPH was assessed. Methods: All patients with presumed NPH were invited to participate in this study. Clinical assessment, MRI, and neuropsychological evaluation were followed by a lumbar CSF tap test consisting of removing 40 ml CSF. When this test resulted in marked clinical improvement of gait impairment, mental disturbances, or both, the patient was shunted without further tests. In patients with either questionable or no improvement after the CSF tap test, ELD was carried out. The value of ELD for predicting the outcome after shunting was calculated by correlating the results of ELD with that of ventriculoperitoneal shunting. Results: Between January 1994 and December 2000, 49 presumed NPH patients from three institutes were included. Forty three had idiopathic, and the remaining six had secondary NPH. Forty eight patients were shunted; 39 had an ELD of whom 38 completed the test. After 2 months 35 of the 48 (73%) shunted patients had improved. The predictive value of a positive ELD was 87% (95% confidence interval (95% CI) 62–98) and that of a negative ELD 36% (95% CI 17–59). In two patients serious test related complications (meningitis) occurred without residual deficit. Conclusion: The study suggests that although the predictive value of a positive ELD is high, that of a negative ELD is deceptively low because of the high rate of false negative results. The costs and invasiveness of the test and the possibility of serious test related complications further limits its usefulness in managing patients with presumed NPH. PMID:11909911

A physical framework for implementing virtual models of intracranial pressure and cerebrospinal fluid dynamics in hydrocephalus shunt testing.

PubMed

Venkataraman, Pranav; Browd, Samuel R; Lutz, Barry R

2016-09-01

OBJECTIVE The surgical placement of a shunt designed to resolve the brain's impaired ability to drain excess CSF is one of the most common treatments for hydrocephalus. The use of a dynamic testing platform is an important part of shunt testing that can faithfully reproduce the physiological environment of the implanted shunts. METHODS A simulation-based framework that serves as a proof of concept for enabling the application of virtual intracranial pressure (ICP) and CSF models to a physical shunt-testing system was engineered. This was achieved by designing hardware and software that enabled the application of dynamic model-driven inlet and outlet pressures to a shunt and the subsequent measurement of the resulting drainage rate. RESULTS A set of common physiological scenarios was simulated, including oscillations in ICP due to respiratory and cardiac cycles, changes in baseline ICP due to changes in patient posture, and transient ICP spikes caused by activities such as exercise, coughing, sneezing, and the Valsalva maneuver. The behavior of the Strata valve under a few of these physiological conditions is also demonstrated. CONCLUSIONS Testing shunts with dynamic ICP and CSF simulations can facilitate the optimization of shunts to be more failure resistant and better suited to patient physiology.

Post ventriculoperitoneal shunt abdominal pseudocyst: Challenges posed in management.

PubMed

Hamid, Raashid; Baba, Aejaz A; Bhat, Nisar A; Mufti, Gowhar; Mir, Younis A; Sajad, Wani

2017-01-01

In patients with hydrocephalus, the abdominal cavity has been used for absorption of cerebrospinal fluid (CSF) since 1905. Ventriculoperitoneal (VP) shunt operation is followed by abdominal complications in about 5-47% cases. Abdominal CSF pseudo cyst is an uncommon, but well described complication. This survey was conducted to study the clinical profile and management of this entity. We present our experience with cases of CSF pseudo cyst in children. Retrospective analysis of 4 cases diagnosed to have abdominal pseudo cyst following VP shunt between 2008 and 2013. All the four cases were suspected clinically and diagnosis was confirmed by abdominal ultrasonography. In three patients, the cyst was multilocular and of varying size. Fourth one had a unilocular cyst at the lower end of VP shunt. All the four patients had features of varying degree raised intracranial pressure and a two patients had abdominal signs also. All the patients needed open exploration. Cyst fluid was drained and partial to complete excision of the cyst was done along with the repositioning of the shunt in abdominal cavity in three patients and exteriorization of shunt in one patient. Patients were followed for any further complication over a period of 1-year. Abdominal pseudo cyst is a rare complication after VP Shunt and could result in shunt malfunction or abdominal symptoms and signs. Whenever suspected it should be confirmed by imaging, followed by open exploration and repositioning of the shunt.

Use of intrathecal urokinase in repeated shunt and external ventricular drain blockage from high CSF protein due to an optic pathway glioma.

PubMed

Shooman, David; Vajramani, Girish V; Davidson, Jennifer; Sparrow, Owen C

2010-05-01

High cerebrospinal fluid (CSF) protein is a recognised association of optic pathway gliomas. This can occlude ventriculoperitoneal (VP) shunt catheters or external ventricular drains (EVD). We describe an 8-year-old boy with an optic pathway glioma, who had frequent episodes of a blocked VP shunt and EVD due to high CSF protein level. This responded favourably to repeated urokinase instillation into the catheter lumen. We present the course of treatment and the method of administration and review the literature behind thrombolytic therapy for occluded catheter devices. Intrathecal urokinase was effective in unblocking the EVD and lysing the protein clots within the ventricle. We found no previously published cases of intrathecal urokinase for this problem. This novel intervention seemed promising as a safe and effective means of maintaining EVD patency in cases complicated by excessive protein loads in CSF and hydrocephalus.

Index of cerebrospinal compensatory reserve in hydrocephalus.

PubMed

Kim, Dong-Joo; Czosnyka, Zofia; Keong, Nicole; Radolovich, Danila K; Smielewski, Peter; Sutcliffe, Michael P F; Pickard, John D; Czosnyka, Marek

2009-03-01

An index of cerebrospinal compensatory reserve (RAP) has been introduced as a potential descriptor of neurological deterioration after head trauma. It is numerically computed as a linear correlation coefficient between the mean intracranial pressure and the pulse amplitude of the pressure waveform. We explore how RAP varies with different forms of physiological or nonphysiological intracranial volume loads in adult hydrocephalus, with and without a functioning cerebrospinal fluid (CSF) shunt. A database of intracranial pressure recordings during CSF infusion studies and overnight monitoring in hydrocephalic patients was reviewed for clinical comparison of homogeneous subgroups of patients with hypothetical differences of pressure-volume compensatory reserve. The database includes 980 patients of mixed etiology: idiopathic normal pressure hydrocephalus (NPH), 47%; postsubarachnoid hemorrhage NPH, 12%; noncommunicating hydrocephalus, 22%; others, 19%. All CSF compensatory parameters were calculated by using intracranial pressure waveforms. In NPH, RAP correlated strongly with the resistance to CSF outflow (r(s) = 0.35; P = 0.045), but weakly correlated with ventriculomegaly (r(s) = 0.13; P = 0.41). In idiopathic nonshunted NPH patients, RAP did not correlate significantly with elasticity calculated from the CSF infusion test (r(s) = 0.11; P = 0.21). During infusion studies, RAP increased in comparison to values recorded at baseline (from a median of 0.45-0.86, P = 0.14 * 10(-8)), indicating a narrowing of the volume-pressure compensatory reserve. During B-waves associated with the REM (rapid eye movement) phase of sleep, RAP increased from a median of 0.53 to 0.89; P = 1.2 * 10(-5). After shunting, RAP decreased (median before shunting, 0.59; median after shunting, 0.34; P = 0.0001). RAP also showed the ability to reflect the functional state of the shunt (patent shunt median, 0.36; blocked shunt median, 0.84; P = 0.0002). RAP appears to characterize pressure-volume compensatory reserve in patients with hydrocephalus.

Post ventriculoperitoneal shunt abdominal pseudocyst: Challenges posed in management

PubMed Central

Hamid, Raashid; Baba, Aejaz A.; Bhat, Nisar A.; Mufti, Gowhar; Mir, Younis A.; Sajad, Wani

2017-01-01

Background: In patients with hydrocephalus, the abdominal cavity has been used for absorption of cerebrospinal fluid (CSF) since 1905. Ventriculoperitoneal (VP) shunt operation is followed by abdominal complications in about 5-47% cases. Abdominal CSF pseudo cyst is an uncommon, but well described complication. Aim: This survey was conducted to study the clinical profile and management of this entity. We present our experience with cases of CSF pseudo cyst in children. Materials and Methods: Retrospective analysis of 4 cases diagnosed to have abdominal pseudo cyst following VP shunt between 2008 and 2013. All the four cases were suspected clinically and diagnosis was confirmed by abdominal ultrasonography. Results: In three patients, the cyst was multilocular and of varying size. Fourth one had a unilocular cyst at the lower end of VP shunt. All the four patients had features of varying degree raised intracranial pressure and a two patients had abdominal signs also. All the patients needed open exploration. Cyst fluid was drained and partial to complete excision of the cyst was done along with the repositioning of the shunt in abdominal cavity in three patients and exteriorization of shunt in one patient. Patients were followed for any further complication over a period of 1-year. Conclusion: Abdominal pseudo cyst is a rare complication after VP Shunt and could result in shunt malfunction or abdominal symptoms and signs. Whenever suspected it should be confirmed by imaging, followed by open exploration and repositioning of the shunt. PMID:28413525

EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients☆

PubMed Central

Aoki, Yasunori; Kazui, Hiroaki; Tanaka, Toshihisa; Ishii, Ryouhei; Wada, Tamiki; Ikeda, Shunichiro; Hata, Masahiro; Canuet, Leonides; Musha, Toshimitsu; Matsuzaki, Haruyasu; Imajo, Kaoru; Yoshiyama, Kenji; Yoshida, Tetsuhiko; Shimizu, Yoshiro; Nomura, Keiko; Iwase, Masao; Takeda, Masatoshi

2013-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or “CSF tapping” is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified “shunt responders” and “shunt nonresponders” with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH. PMID:24273735

EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients.

PubMed

Aoki, Yasunori; Kazui, Hiroaki; Tanaka, Toshihisa; Ishii, Ryouhei; Wada, Tamiki; Ikeda, Shunichiro; Hata, Masahiro; Canuet, Leonides; Musha, Toshimitsu; Matsuzaki, Haruyasu; Imajo, Kaoru; Yoshiyama, Kenji; Yoshida, Tetsuhiko; Shimizu, Yoshiro; Nomura, Keiko; Iwase, Masao; Takeda, Masatoshi

2013-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or "CSF tapping" is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified "shunt responders" and "shunt nonresponders" with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.

Comparison of anti-siphon devices-how do they affect CSF dynamics in supine and upright posture?

PubMed

Gehlen, Manuel; Eklund, Anders; Kurtcuoglu, Vartan; Malm, Jan; Schmid Daners, Marianne

2017-08-01

Three different types of anti-siphon devices (ASDs) have been developed to counteract siphoning-induced overdrainage in upright posture. However, it is not known how the different ASDs affect CSF dynamics under the complex pressure environment seen in clinic due to postural changes. We investigated which ASDs can avoid overdrainage in upright posture best without leading to CSF accumulation. Three shunts each of the types Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane controlled) were tested. The shunts were compared on a novel in vitro setup that actively emulates the physiology of a shunted patient. This testing method allows determining the CSF drainage rates, resulting CSF volume, and intracranial pressure in the supine, sitting, and standing posture. The flow-regulated ASDs avoided increased drainage by closing their primary flow path when drainage exceeded 1.39 ± 0.42 mL/min. However, with intraperitoneal pressure increased in standing posture, we observed reopening of the ASD in 3 out of 18 experiment repetitions. The adjustable gravitational ASDs allow independent opening pressures in horizontal and vertical orientation, but they did not provide constant drainage in upright posture (0.37 ± 0.03 mL/min and 0.26 ± 0.03 mL/min in sitting and standing posture, respectively). Consequently, adaptation to the individual patient is critical. The membrane-controlled ASDs stopped drainage in upright posture. This eliminates the risk of overdrainage, but leads to CSF accumulation up to the volume observed without shunting when the patient is upright. While all tested ASDs reduced overdrainage, their actual performance will depend on a patient's specific needs because of the large variation in the way the ASDs influence CSF dynamics: while the flow-regulated shunts provide continuous drainage in upright posture, the gravitational ASDs allow and require additional adaptation, and the membrane-controlled ASDs show robust siphon prevention by a total stop of drainage.

Quality measurement in the shunt treatment of hydrocephalus: analysis and risk adjustment of the Revision Quotient.

PubMed

Piatt, Joseph H; Freibott, Christina E

2014-07-01

OBJECT.: The Revision Quotient (RQ) has been defined as the ratio of the number of CSF shunt revisions to the number of new shunt insertions for a particular neurosurgical practice in a unit of time. The RQ has been proposed as a quality measure in the treatment of childhood hydrocephalus. The authors examined the construct validity of the RQ and explored the feasibility of risk stratification under this metric. The Kids' Inpatient Database for 1997, 2000, 2003, 2006, and 2009 was queried for admissions with diagnostic codes for hydrocephalus and procedural codes for CSF shunt insertion or revision. Revision quotients were calculated for hospitals that performed 12 or more shunt insertions annually. The univariate associations of hospital RQs with a variety of institutional descriptors were analyzed, and a generalized linear model of the RQ was constructed. There were 12,244 admissions (34%) during which new shunts were inserted, and there were 23,349 admissions (66%) for shunt revision. Three hundred thirty-four annual RQs were calculated for 152 different hospitals. Analysis of variance in hospital RQs over the 5 years of study data supports the construct validity of the metric. The following factors were incorporated into a generalized linear model that accounted for 41% of the variance of the measured RQs: degree of pediatric specialization, proportion of initial case mix in the infant age group, and proportion with neoplastic hydrocephalus. The RQ has construct validity. Risk adjustment is feasible, but the risk factors that were identified relate predominantly to patterns of patient flow through the health care system. Possible advantages of an alternative metric, the Surgical Activity Ratio, are discussed.

Early postnatal cranial vault reduction and fixation surgery for severe hydrocephalic macrocephaly.

PubMed

Iyer, Rajiv R; Carey, Carolyn M; Rottgers, S Alex; Tetreault, Lisa; Shimony, Nir; Katzenstein, Jennifer; Ruas, Ernesto; Tuite, Gerald F

2018-05-01

OBJECTIVE Infants with severe hydrocephalus and extreme macrocephaly typically undergo CSF diversion early in life, which can result in significant cranial deformity due to CSF overdrainage. In this scenario, overlap of the cranial plates can precede the development of secondary synostosis and/or severe, permanent cranial deformity. As a result, extensive cranial vault remodeling is sometimes undertaken later in life, which is often challenging and has been associated with mortality and a high morbidity rate. The authors have previously described a technique for early postnatal cranial vault reduction and fixation (CVRF), in which the calvarial bones are stabilized using absorbable fixation plates in the neonatal period, in an attempt to facilitate patient positioning, simplify hydrocephalus management, and improve cosmesis. Here, the authors describe their institutional experience managing patients with extreme neonatal hydrocephalus with CSF diversion, with and without CVRF, over the past 12 years. METHODS The authors retrospectively reviewed the charts of infants with extreme hydrocephalus (head circumference > 49 cm) treated at their children's hospital with ventriculoperitoneal shunting, with or without CVRF, between 2005 and 2017. Data collected included age, sex, etiology of hydrocephalus, type of CVRF performed (anterior, posterior, or combined), follow-up duration, orbitofrontal circumference, craniometric measurements, intraoperative blood loss, operative duration, and postoperative complications. Developmental data were collected using the third edition of the Ages and Stages Questionnaire. Photographic imaging was used to demonstrate esthetic outcomes, and family questionnaires were used to evaluate satisfaction with the esthetic outcome. RESULTS Eleven patients with extreme neonatal hydrocephalus underwent CSF shunting; 5 underwent shunting alone and 6 patients underwent shunting and CVRF. For patients who underwent shunting and CVRF, the median age at CVRF was 6 days and the median interval between shunt placement and CVRF was 2.5 days. The mean extent of calvarial vault volume reduction was 44.5% (± 3.9%). The mean duration of the CVRF procedure was 108 minutes, and 5 of 6 patients required intraoperative transfusion. Of the 5 patients who underwent shunting alone, 3 developed severe cranial deformities. Of 6 patients who underwent shunting and CVRF, 1 had a poor cosmetic outcome. In the shunting-alone group, 2 patients died and 1 required extensive cranial vault correction at 10 years of age. One patient in the shunting and CVRF group also died. CONCLUSIONS CVRF in combination with CSF shunting in the neonatal period can simplify the treatment of the rare case of severe hydrocephalic macrocephaly and leads to cosmetic outcomes that are considered good by their families.

Progressive Functional Underdrainage in Cerebrospinal Fluid Shunt-Dependent Women During Pregnancy: Case Report and Review of the Literature.

PubMed

Krauss, Philipp; Fritz-Naville, Marco; Regli, Luca; Stieglitz, Lennart Henning

2018-01-01

Since the 1950s cerebrospinal fluid (CSF) shunt dependency has no longer been a contradiction to normal life, including sexuality and pregnancy in women, because of advances in the understanding of hydrocephalus and shunt technology. Although pregnancy in shunt-dependent women is rare, it causes uncertainty among treating physicians. We report the case of a 34-year-old pregnant woman with a ventriculoperitoneal shunt. Throughout her pregnancy she experienced progressive symptoms of CSF underdrainage without any signs of other pregnancy-related complications. After the delivery of a healthy infant, shunt resistance had to be readjusted to prepregnancy levels. A comprehensive review of the literature reports in English, listed in PubMed, is provided. Conservative treatment of pregnancy-related functional underdrainage by consecutive valve pressure adjustment is possible, easy, and safe. Copyright © 2017 Elsevier Inc. All rights reserved.

The predictive value of ventricular CSF removal in normal pressure hydrocephalus.

PubMed

Krauss, J K; Regel, J P

1997-08-01

We report the impact of diagnostic ventricular CSF removal (VCR) on the gait disturbance in 24 patients with suspected normal pressure hydrocephalus (NPH) who had an intraventricular catheter for studies of CSF dynamics in order to select patients for shunt surgery. There were no complications related to removal of 24 ml CSF over a period of 6 hours in four instances or to the removal of 15-18 ml at one time in twenty instances. Seventeen out of 24 patients were diagnosed as having NPH. Two of those patients who had relatively mild symptoms had a prolonged amelioration of their gait disturbance after diagnostic VCR. Thirteen patients underwent subsequent shunt operations. Eleven of them had good functional and symptomatic improvement on follow-up. In those six patients who had a marked amelioration of their gait disturbance after diagnostic VCR, not only improvement of the gait disturbance was observed after shunting, but a consistent overall improvement as well. The predictive value of VCR was more variable in those six patients who had only a moderate response to VCR. No change of the gait disturbance after VCR was noted in seven patients in whom the diagnosis of NPH was not confirmed. Diagnostic VCR might be a valuable ancillary test in specialized centers which routinely use intraventricular CSF monitoring in the selection of patients for shunt surgery.

Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial advancement in the Crouzon syndrome.

PubMed

Panuganti, Bharat A; Leach, Matthew; Antisdel, Jastin

2015-01-01

Cerebrospinal fluid (CSF) rhinorrhea and encephaloceles are rare complications of craniofacial advancement procedures performed in patients with craniofacial dysostoses (CD) to address the ramifications of their midface hypoplasia including obstructed nasal airway, exorbitism, and impaired mastication. Surgical repair of this CSF rhinorrhea is complicated by occult elevations in intracranial pressure (ICP), potentially necessitating open, transcranial repair. We report the first case in otolaryngology literature of a patient with Crouzon syndrome with late CSF rhinorrhea and encephalocele formation after previous LeFort III facial advancement surgery. Describe the case of a patient with Crouzon syndrome who presented with CSF rhinorrhea and encephaloceles as complications of Le Fort III facial advancement surgery. Review the literature pertaining to the incidence and management of post-operative CSF rhinorrhea and encephaloceles. Analyze issues related to repair of these complications, including occult elevations in ICP, the utility of perioperative CSF shunts, and the importance of considering alternative repair schemes to the traditional endonasal, endoscopic approach. Review of the literature describing CSF rhinorrhea and encephalocele formation following facial advancement in CD, focusing on management strategies. CSF rhinorrhea and encephalocele formation are rare complications of craniofacial advancement procedures. Occult elevations in ICP complicate the prospect of permanent surgical repair, potentially necessitating transcranial repair and the use of CSF shunts. Though no consensus exists regarding the utility of perioperative CSF drains, strong associations exist between elevated ICP and failed surgical repair. Additionally, the anatomic changes in the frontal and ethmoid sinuses after facial advancement present a challenge to endoscopic repair. Otolaryngologists should be aware of the possibility of occult elevations in ICP and sinonasal anatomic abnormalities when repairing CSF rhinorrhea in patients with CD. Clinicians should consider CSF shunt placement and carefully weigh the advantages of the transcranial approach versus endonasal, endoscopic techniques.

A novel method for passing cerebrospinal fluid shunt tubing: a proof of principle study.

PubMed

Tubbs, R Shane; Goodrich, Dylan; Tubbs, Isaiah; Loukas, Marios; Cohen-Gadol, Aaron A

2014-12-01

Few innovations in the method of tunneling shunt tubing for cerebrospinal fluid (CSF) shunt diversion have been made since this treatment of hydrocephalus was first developed. Therefore, this feasibility study was performed with the hope of identifying an improved technique that could potentially carry fewer complications. On 10 cadaver sides and when placed in the supine position, small skin incisions were made at the clavicle and ipsilateral subcostal region, and magnets were used to pass standard shunt tubing between the two incisions. Nickel-plated magnets were less effective in pulling the shunt tubing below the skin compared with ceramic magnets. Of these, magnets with pull strengths of 150-200 lbs were the most effective in dragging the subcutaneous tubing between the two incisions. No obvious damage to the skin from the overlying magnet was seen in any specimen. Few options exist for tunneling distal shunt tubing for CSF shunt procedures. Future patient studies are needed to determine if the technique described herein is superior to current methods, particularly when examining patient groups that are at a greater risk for injury during tunneling shunt catheters.

Cerebrospinal fluid volume measurements in hydrocephalic rats.

PubMed

Basati, Sukhraaj; Desai, Bhargav; Alaraj, Ali; Charbel, Fady; Linninger, Andreas

2012-10-01

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Baseline neuropsychological profile and cognitive response to cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus.

PubMed

Thomas, George; McGirt, Matthew J; Woodworth, Graeme; Heidler, Jennifer; Rigamonti, Daniele; Hillis, Argye E; Williams, Michael A

2005-01-01

To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure monitoring and positive response in any of the NPH symptoms following large volume CSF drainage. Forty-two INPH patients underwent neurocognitive testing and Folstein Mini-Mental State Examination (MMSE) prior to shunting. Neurocognitive testing or MMSEwere performed at least 3 months after shunt insertion. Significant improvement in a neurocognitive subtest was defined as improvement by one standard deviation (1 SD) for the patient's age, sex and education level. Significant improvement in overall neurocognitive outcome was defined as a 4-point improvement in MMSE or improvement by 1 SD in 50% of the administered neurocognitive subtests. Nonparametric tests were used to assess changes. Predictors of outcome were assessed via logistic regression analysis. Twenty-two patients (52.3%) showed overall neurocognitive improvement, and significant improvement was seen in tests of verbal memory and psychomotor speed. Predictive analysis showed that patients scoring more than 1 SD below mean at baseline on verbal memory immediate recall were fourfold less likely to show overall cognitive improvement, and sixfold less likely if also associated with visuoconstructional deficit or executive dysfunction. Verbal memory scores at baseline were higher in patients who showed overall cognitive improvement. Shunting INPH patients on the basis of CSF pressure monitoring and drainage response shows a significant rate of cognitive improvement, and baseline neurocognitive test scores may distinguish patients likely to respond to shunt surgery from those who will not. Copyright (c) 2005 S. Karger AG, Basel.

[Extracorporeal ventriculoatrial shunt with the use of one-way ball valve].

PubMed

Kubo, Shigeki; Takimoto, Hiroshi; Hosoi, Kazuki; Toyota, Shingo; Takakura, Shuji; Hayashi, Yasuhiro; Ueno, Masato; Morisako, Toshitaka; Karasawa, Jun; Ninaga, Hideo; Yoshimine, Toshiki

2002-04-01

We developed a simple system of an "extracorporeal" ventriculoatrial (VA) shunt using a one-way ball valve (Acty valve II, Kaneka Medix) to release the patient from postoperative constraint during the ventricular drainage. The system is constructed in such a way that the ventricular drainage tube is connected to the central venous catheter via a one-way valve. The CSF is regulated by using the valve and is diverted into the systemic circulation as in the conventional ventriculoatrial shunt. After 2 or 3 weeks of CSF diversion through the extracorporeal VA shunt, a ventriculoperitoneal shunt is placed if hydrocephalus is apparent by temporary occlusion of the system. We applied this system to 4 patients with hydrocephalus, and we found it useful and free from adverse effects. The patient was freed from physical constraint involved in conventional ventricular drainage and an effective program of early rehabilitation was able to be started.

Impedance Changes Indicate Proximal Ventriculoperitoneal Shunt Obstruction In Vitro.

PubMed

Basati, Sukhraaj; Tangen, Kevin; Hsu, Ying; Lin, Hanna; Frim, David; Linninger, Andreas

2015-12-01

Extracranial cerebrospinal fluid (CSF) shunt obstruction is one of the most important problems in hydrocephalus patient management. Despite ongoing research into better shunt design, robust and reliable detection of shunt malfunction remains elusive. The authors present a novel method of correlating degree of tissue ingrowth into ventricular CSF drainage catheters with internal electrical impedance. The impedance based sensor is able to continuously monitor shunt patency using intraluminal electrodes. Prototype obstruction sensors were fabricated for in-vitro analysis of cellular ingrowth into a shunt under static and dynamic flow conditions. Primary astrocyte cell lines and C6 glioma cells were allowed to proliferate up to 7 days within a shunt catheter and the impedance waveform was observed. During cell ingrowth a significant change in the peak-to-peak voltage signal as well as the root-mean-square voltage level was observed, allowing the impedance sensor to potentially anticipate shunt malfunction long before it affects fluid drainage. Finite element modeling was employed to demonstrate that the electrical signal used to monitor tissue ingrowth is contained inside the catheter lumen and does not endanger tissue surrounding the shunt. These results may herald the development of "next generation" shunt technology that allows prediction of malfunction before it affects patient outcome.

Theoretical considerations on the pathophysiology of normal pressure hydrocephalus (NPH) and NPH-related dementia.

PubMed

Hamlat, Abderrahmane; Adn, Mahmoudreza; Sid-ahmed, Seddik; Askar, Brahim; Pasqualini, Edouardo

2006-01-01

Normal pressure hydrocephalus (NPH) is considered to be an example of reversible dementia although clinical improvement after shunting varies from subject to subject, and recent studies have pointed to a possible link with other dementia. The authors consider that the craniospinal compartment is a partially closed sphere with control device systems represented by the spinal axis and the sagittal sinus-arachnoid villi complex which interact with each other in the clinical patient setting. We hypothesise that changing spinal compliance by altering the flow process and CSF dynamics lead to hydrocephalus. Therefore four NPH types have been distinguished according to the alterations in spinal compliance, decrease in CSF absorption at the sagittal sinus or both occurrences. The authors consider that NPH and NPH-related diseases (NPH-RD) are initiated by the same common final pathway and demonstrate that NPH could represent an initial stage of NPH-RD. Progression of clinical signs can be explained as damage to the cerebral tissue by both intermittent increased intracranial pressure and pulse pressure waves leading to periventricular ischaemia. In addition, they believe that both volume equilibrium and spinal compliance are restored in patients who improve after CSF shunt, whereas in patients whose condition does not improve, only volume equilibrium is restored and not spinal compliance, which was the underlying cause of hydrocephalus in such cases. They therefore wonder whether cervical decompression should not be indicated in patients who show no improvement. Although attractive, this analysis warrants confirmation from clinical, radiological, and hydrodynamic studies.

Extrapyramidal signs in normal pressure hydrocephalus: an objective assessment

PubMed Central

Mandir, Allen S; Hilfiker, Jennifer; Thomas, George; Minahan, Robert E; Crawford, Thomas O; Williams, Michael A; Rigamonti, Daniele

2007-01-01

Background Beyond the classic Normal Pressure Hydrocephalus (NPH) triad of gait disturbance, incontinence, and dementia are characteristic signs of motor dysfunction in NPH patients. We used highly sensitive and objective methods to characterize upper limb extrapyramidal signs in a series of NPH subjects compared with controls. Concentrated evaluation of these profound, yet underappreciated movement disorders of NPH before and after techniques of therapeutic intervention may lead to improved diagnosis, insight into pathophysiology, and targeted treatment. Methods Twenty-two (22) consecutive NPH patients and 17 controls performed an upper limb motor task battery where highly sensitive and objective measures of akinesia/bradykinesia, tone, and tremor were conducted. NPH subjects performed this test battery before and more than 36 h after continuous CSF drainage via a spinal catheter over 72 h and, in those subjects undergoing permanent ventriculo-peritoneal shunt placement, at least 12 weeks later. Control subjects performed the task battery at the same dates as the NPH subjects. Statistical analyses were applied to group populations of NPH and control subjects and repeated measures for within subject performance. Results Twenty (20) NPH subjects remained in the study following CSF drainage as did 14 controls. NPH subjects demonstrated akinesia/bradykinesia (prolonged reaction and movement times) and increased resting tone compared with controls. Furthermore, the NPH group demonstrated increased difficulty with self-initiated tasks compared with stimulus-initiated tasks. Following CSF drainage, some NPH subjects demonstrated reduced movement times with greater improvement in self- versus stimulus-initiated tasks. Group reaction time was unchanged. Resting tremor present in one NPH subject resolved following shunt placement. Tone measures were consistent for all subjects throughout the study. Conclusion Clinical motor signs of NPH subjects extend beyond gait deficits and include extrapyramidal manifestations of bradykinesia, akinesia, rigidity, and propensity to perform more poorly when external cues to move are absent. Objective improvement of some but not all of these features was seen following temporary or permanent CSF diversion. PMID:17697324

An 8-month history of meningitis in an extremely low birth weight infant? - Long-lasting Infection with Ureaplasma parvum.

PubMed

Glaser, K; Wohlleben, M; Speer, C P

2015-02-01

Ureaplasma spp. have been implicated in the pathogenesis of both preterm labor and neonatal morbidity including pneumonia and sepsis and the development of chronic lung disease of prematurity. Data on Ureaplasma meningitis are limited and partly controversially discussed. We report the unique case of a 9-month-old infant with progressive internal hydrocephalus of unknown origin and developmental delay due to a history of>200 days of inflammation of the central nervous system. The female extremely low birth weight infant had been referred to our hospital for ventriculoperitoneal shunt implantation. She had been born at 26+3 weeks of gestation with a birth weight of 940 g. With the exception of a moderate respiratory distress syndrome, postnatal period had been reported uneventful. However, internal hydrocephalus had become manifest at 4 weeks of postnatal age. Intraventricular hemorrhage had not been documented by cranial ultrasound and magnetic resonance imaging. Cerebrospinal fluid (CSF) analysis had repetitively revealed pronounced inflammation reflected by pleocytosis (50-86 leukocytes/μL, 60% lymphocytes), CSF protein levels of 578-1,026 mg/dL and undetectable CSF glucose. Although suggesting bacterial meningitis, microbial diagnostics had not been indicative, and empirical antibiotics had not affected the CSF findings. On admission to our hospital, CSF analysis still documented significant inflammation (125 leukocytes/μL, CSF protein 565 mg/dL, CSF glucose<2 mg/dL). Due to a prenatal history of cerclage, we initiated microbial diagnostics on Ureaplasma spp. and Mycoplasma hominis. U. parvum was detected in CSF by culture and PCR, no other pathogens were isolated. On intravenous treatment with chloramphenicol, CSF profile continuously normalized, and cultures and PCR became negative. Treatment was continued for 3 weeks, and the infant was discharged after uncomplicated ventriculoperitoneal shunt placement. During a 12-month observation period she has shown encouraging recovery. In preterm infants, in particular, internal hydrocephalus of unknown origin and sustained CSF inflammation are highly suggestive of Ureaplasma meningitis. Our case highlights that infection may escape detection if not explicitly considered, since microbial diagnosis requires complex media and PCR. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of ventricular and lumbar cerebrospinal fluid T cells in non-inflammatory neurological disorder (NIND) patients.

PubMed

Provencio, J Javier; Kivisäkk, Pia; Tucky, Barbara H; Luciano, Mark G; Ransohoff, Richard M

2005-06-01

The aim of the present study was to define the cellular composition of ventricular, as compared with lumbar, cerebrospinal fluid (CSF) in patients with non-inflammatory neurological disorders (NIND). We addressed this issue by determining the cellular composition of lumbar CSF from patients with normal pressure hydrocephalus (NPH) who were undergoing lumbar CSF drainage during evaluation for shunting procedures, and evaluating ventricular CSF from a subset of these who underwent subsequent placement of ventriculoperitoneal shunts. We determined the cellular composition of lumbar CSF from 18 patients with NPH, and found that the leukocyte differentials, and relative proportions of CD4+ and CD8+ central memory (TCM), effector memory (TEM) and naive cell (TNaive) populations, were equivalent to those found previously in studies of CSF from patients with NIND. We further evaluated cells in the ventricular CSF of five patients who had previously undergone lumbar drainage. Leukocyte differential counts, as well as CD4+ and CD8+ TCM, TEM, and TNaive proportions, were equivalent in matched ventricular and lumbar CSF samples. These observations support the hypothesis that leukocytes enter the CSF in a selective fashion, at its site of formation in the choroid plexus. The results implicate CSF T cells in the immune surveillance of the central nervous system.

Pediatric neurosurgical practice patterns designed to prevent cerebrospinal fluid shunt infection.

PubMed

Gruber, Thomas J; Riemer, Sara; Rozzelle, Curtis J

2009-01-01

Various factors have been associated with cerebrospinal fluid (CSF) shunt infection risk, leading to many recommendations intended to reduce that risk. We sought to assess current North American pediatric neurosurgical practice patterns in this regard via a web-based survey. Particular attention was paid to the use of antibiotic-impregnated materials and prophylactic perioperative antibiotics. The membership of the section on pediatric neurological surgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons was invited to complete a survey of current practices intended to minimize CSF shunt infection risk. To be eligible for participation in this study, the respondent had to maintain an active neurosurgical practice within North America and place or revise at least 25 shunts in pediatric patients (<21 years) per year. Responses to the questionnaire were then analyzed. A total of 100 responses were analyzed. All respondents were familiar with antibiotic-impregnated shunt catheters, and 61 of 100 had actually used them. Eleven of 61 respondents use them universally, 20 of 61 in >50% of cases, and 30 of 61 in <50% of cases. Antibiotic-impregnated suture material was known to 59% of respondents, of whom 28% (14 of 59) reported having actually used antimicrobial suture. All respondents use perioperative intravenous antibiotics with vancomycin, first-generation cephalosporins, and then second-generation cephalosporins being the most common. Routine use of intraventricular antibiotics was reported by 27%. An assessment of surgical techniques revealed that 90% limit shunt contact with patient's skin, 62% use the double-gloving technique, 45% handle shunt components only with instruments, and 34% use an antiseptic shampoo preoperatively. Our survey reveals a wide range of practices intended to prevent shunt infection and captures, in particular, current trends in the use of antibiotic-impregnated materials and perioperative antibiotics for CSF shunting procedures. Copyright 2010 S. Karger AG, Basel.

Normal pressure hydrocephalus: Diagnostic and predictive evaluationon

PubMed Central

Damasceno, Benito Pereira

2009-01-01

In typical cases, normal pressure hydrocephalus (NPH) manifests itself with the triad of gait disturbance, which begins first, followed by mental deterioration and urinary incontinence associated with ventriculomegaly (on CT or MRI) and normal cerebrospinal fluid (CSF) pressure. These cases present minor diagnostic difficulties and are the most likely to improve after shunting. Problems arise when NPH shows atypical or incomplete clinical manifestations (25–50% of cases) or is mimicked by other diseases. In this scenario, other complementary tests have to be used, preferentially those that can best predict surgical outcome. Radionuclide cisternography, intracranial pressure monitoring (ICP) and lumbar infusion tests can show CSF dynamics malfunction, but none are able to confirm whether the patient will benefit from surgery. The CSF tap test (CSF-TT) is the only procedure that can temporarily simulate the effect of definitive shunt. Since the one tap CSF-TT has low sensitivity, it cannot be used to exclude patients from surgery. In such cases, we have to resort to a repeated CSF-TT (RTT) or continuous lumbar external drainage (LED). The most reliable prediction would be achieved if RTT or LED proved positive, in addition to the occurrence of B-waves during more than 50% of ICP recording time. This review was based on a PubMed literature search from 1966 to date. It focuses on clinical presentation, neuroimaging, complementary prognostic tests, and differential diagnosis of NPH, particularly on the problem of selecting appropriate candidates for shunt. PMID:29213603

The predictive value of external continuous lumbar drainage, with cerebrospinal fluid outflow controlled by medium pressure valve, in normal pressure hydrocephalus.

PubMed

Panagiotopoulos, V; Konstantinou, D; Kalogeropoulos, A; Maraziotis, T

2005-09-01

Although sporadic studies have described temporary external cerebrospinal fluid (CSF) lumbar drainage as a highly accurate test for predicting the outcome after ventricular shunting in normal pressure hydrocephalus (NPH) patients, a more recent study reports that the positive predictive value of external lumbar drainage (ELD) is high but the negative predictive value is deceptively low. Therefore, we conducted a prospective study in order to evaluate the predictive value of a continuous ELD, with CSF outflow controlled by medium pressure valve, in NPH patients. Twenty-seven patients with presumed NPH were admitted to our department and CSF drainage was carried out by a temporary (ELD) with CSF outflow controlled by a medium pressure valve for five days. All patients received a ventriculoperitoneal shunt using a medium pressure valve based upon preoperative clinical and radiographic criteria of NPH, regardless of ELD outcome. Clinical evaluation of gait disturbances, urinary incontinence and mental status, and radiological evaluation with brain CT was performed prior to and after ELD test, as well as three months after shunting. Twenty-two patients were finally shunted and included in this study. In a three-month follow-up, using a previously validated score system, overall improvement after permanent shunting correlated well to improvement after ELD test (Spearman's rho = 0.462, p = 0.03). When considering any degree of improvement as a positive response, ELD test yielded high positive predictive values for all individual parameters (gait disturbances 94%, 95% CI 71%-100%, urinary incontinence 100%, 95% CI 66%-100%, and mental status 100%, 95% CI 66%-100%) but negative predictive values were low (< 50%) except for cognitive impairment (85%, 95% CI 55%-98%). This study suggests that a positive ELD-valve system test should be considered a reliable criterion for preoperative selection of shunt-responsive NPH patients. In case of a negative ELD-valve system test, further investigation of the presumed NPH patients with additional tests should be performed.

Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting.

PubMed

Schmidt, Martin J; Rummel, Christoph; Hauer, Jessica; Kolecka, Malgorzata; Ondreka, Nele; McClure, Vanessa; Roth, Joachim

2016-06-29

Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL-6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo-peritoneal shunt (VP-shunt) treatment. The concentrations of AQP4 and IL-6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF. Brain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis.

Poor correlation between head circumference and cranial ultrasound findings in premature infants with intraventricular hemorrhage.

PubMed

Ingram, Martha-Conley E; Huguenard, Anna L; Miller, Brandon A; Chern, Joshua J

2014-08-01

Intraventricular hemorrhage (IVH) is the most common cause of hydrocephalus in the pediatric population and is particularly common in preterm infants. The decision to place a ventriculoperitoneal shunt or ventricular access device is based on physical examination findings and radiographic imaging. The authors undertook this study to determine if head circumference (HC) measurements correlated with the Evans ratio (ER) and if changes in ventricular size could be detected by HC measurements. All cranial ultrasound (CUS) reports at the authors' institution between 2008 and 2011 were queried for terms related to hydrocephalus and IVH, from which a patient cohort was determined. A review of radiology reports, HC measurements, operative interventions, and significant clinical events was performed for each patient in the study. Additional radiographic measurements, such as an ER, were calculated by the authors. Significance was set at a statistical threshold of p < 0.05 for this study. One hundred forty-four patients were studied, of which 45 (31%) underwent CSF diversion. The mean gestational age and birth weight did not differ between patients who did and those who did not undergo CSF diversion. The CSF diversion procedures were reserved almost entirely for patients with IVH categorized as Grade III or IV. Both initial ER and HC were significantly larger for patients who underwent CSF diversion. The average ER and HC at presentation were 0.59 and 28.2 cm, respectively, for patients undergoing CSF diversion, and 0.34 and 25.2 cm for those who did not undergo CSF diversion. There was poor correlation between ER and HC measurements regardless of gestational age (r = 0.13). Additionally, increasing HC was not found to correlate with increasing ERs on consecutive CUSs (φ = -0.01, p = 0.90). Patients who underwent CSF diversion after being followed with multiple CUSs (10 of 45 patients) presented with smaller ERs and HC than those who underwent CSF diversion after a single CUS. Just prior to CSF diversion surgery, the patients who received multiple CUSs had ERs, but not HC measurements, that were similar to those in patients who underwent CSF diversion after a single CUS. The HC measurement does not correlate with the ER or with changes in ER and therefore does not appear to be an adequate surrogate for serial CUSs. In patients who are followed for longer periods of time before CSF shunting procedures, the ER may play a larger role in the decision to proceed with surgery. Clinicians should be aware that the ER and HC are not surrogates for one another and may reflect different pathological processes. Future studies that take into account other physical examination findings and long-term clinical outcomes will aid in developing standardized protocols for evaluating preterm infants for ventriculoperitoneal shunt or ventricular access device placement.

[Intracranial pressure monitoring and CSF dynamics in patients with neurological disorders: indications and practical considerations].

PubMed

Poca, M; Sahuquillo, J

2001-01-01

The study of cerebrospinal fluid (CSF) dynamics is central to the diagnosis of adult chronic hydrocephalus (ACH). At present, many neurology and neurosurgery departments use one or more tests to guide diagnosis of this syndrome and to predict patient response to shunting. In specialised centres, the study of CSF dynamics is combined with continuous intracranial pressure (ICP) monitoring. Determination of several variables of CSF dynamics and definitions of qualitative and quantitative characteristics of ICP can be used to establish whether the hydrocephalus is active, compensated or arrested. CSF dynamics and ICP monitoring can also be used to check the correct functioning of the shunt and can be of use in the clinical management of patients with pseudotumor cerebri. Moreover, ICP monitoring is used to guide the treatment of several acute neurological processes. The aim of this review is to describe the fundamentals of CSF dynamics studies and the bases of continuous ICP monitoring. The advantages and disadvantages of several hydrodynamic tests that can be performed by lumbar puncture, as well as the normal and abnormal characteristics of an ICP recording, are discussed.

[Successful treatment of Candida meningitis with miconazole].

PubMed

Fukui, S; Tabata, H; Hayashi, H; Matsushima, Y

1990-09-01

This paper presents a case of successful treatment of candida meningitis with miconazole. A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986. Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH. Candida albicans was cultured from her CSF. The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations. Combination therapy (amphotericin B and flucytosine) was initiated. However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B. Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200-1200 mg/day, total 70.4 g) was begun on November 23. Clinical and CSF findings were improved soon. No side effect of miconazole was observed. After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987. Reports of mycosis in central nervous system are recently increasing, especially for candidosis. Cryptococcosis is noted frequently as an opportunistic infection of AIDS. The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis. Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance. Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis. Few side effects have been reported with its use. The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of cerebrospinal fluid flow rates measured by phase-contrast MR to predict outcome of ventriculoperitoneal shunting for idiopathic normal-pressure hydrocephalus.

PubMed

Dixon, Geoffrey R; Friedman, Jonathan A; Luetmer, Patrick H; Quast, Lynn M; McClelland, Robyn L; Petersen, Ronald C; Maher, Cormac O; Ebersold, Michael J

2002-06-01

To determine whether favorable clinical response and magnitude of improvement are associated with increased aqueductal cerebrospinal fluid (CSF) flow rates in patients who undergo ventriculoperitoneal shunting (VPS) for idiopathic normal-pressure hydrocephalus (NPH). Between January 1995 and June 2000, 49 patients (14 men and 35 women; mean age, 72.9 years; range, 54-88 years) underwent magnetic resonance quantification of aqueductal CSF flow followed by VPS for presumed idiopathic NPH at the Mayo Clinic, Rochester, Minn. Logistic regression models for the odds of any improvement in score as a function of aqueductal CSF flow and separate models for any improvement in gait, incontinence, cognition, and total score were constructed. Forty-two patients (86%) had improvement in gait at postoperative follow-up (mean, 10 months). Of the 32 patients with incontinence, 27 (69%) improved. Of the 36 patients with cognitive impairment, 16 (44%) improved. In univariate and fully adjusted models, increased CSF flow through the aqueduct was not significantly associated with improvement or the magnitude of improvement in gait, cognition, or incontinence. Thirty-six patients underwent high-volume lumbar puncture preoperatively, of whom 5 (14%) had no response. The aqueductal CSF flow rates of these 5 patients were significantly higher than those of the patients who improved after lumbar puncture. Postoperative complications occurred in 15 patients. The aqueductal CSF flow rates in these 15 patients were not significantly different from those of patients who experienced no complications. Among patients who underwent VPS for the treatment of NPH, measurement of CSF flow through the cerebral aqueduct did not reliably predict which patients would improve after shunting or the magnitude of improvement.

Glaucoma in patients with shunt-treated normal pressure hydrocephalus.

PubMed

Gallina, Pasquale; Savastano, Alfonso; Becattini, Eleonora; Orlandini, Simone; Scollato, Antonio; Rizzo, Stanislao; Carreras, Giulia; Di Lorenzo, Nicola; Porfirio, Berardino

2017-11-17

OBJECTIVE Changes in the pressure gradient between intraocular and intracranial compartments at the lamina cribrosa level are a possible explanation of normal tension glaucoma (NTG). Shunt-treated normal pressure hydrocephalus (NPH) is a model for testing whether the increase (time from disease onset to CSF shunt placement, i.e., "protection period") and decrease (time from shunt placement to observation, i.e., "exposure period") in intracranial pressure (ICP) are glaucoma protective or risk factors, respectively. The authors estimated the prevalence of NTG in patients with shunt-treated NPH and calculated the extent of optic nerve exposure to changes in the trans-lamina cribrosa gradient. METHODS Data obtained in patients with NPH who had undergone ventriculoperitoneal (VP) shunt placement were analyzed. Patients with more than 6 months' follow-up, no pathologies associated with ICP changes or CSF dynamics disturbances, and no surgical or valve-related complications were scheduled for ophthalmic evaluation. RESULTS Nine of 22 patients had NTG, which is about a 40-fold increase in rate compared with the rate in the general elderly population without hydrocephalus (p < 0.001). The median protection period was 12.0 months in patients with NTG and 18.0 months in those without NTG (p = 0.033). The median ICP decrease multiplied by duration of exposure in months was 76.0 mm Hg × months in the NTG group and 24.1 mm Hg × months in the no-NTG group (p = 0.048). The patients' median adjusted age (adjusted for "protection" and "exposure" times) was 85.1 years in the NTG group and 78.8 years in the no-NTG group (p = 0.001). CONCLUSIONS A crucial risk factor for development of NTG in patients with shunt-treated NPH is the duration of optic nerve exposure to the lowering of ICP. Patients with NPH who are candidates for CSF shunting should be informed of the risk of incurring glaucoma. Longitudinal studies could provide estimates of tolerated times for a given ICP decrease.

Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement

PubMed Central

Tulipan, Noel; Wellons, John C.; Thom, Elizabeth A.; Gupta, Nalin; Sutton, Leslie N.; Burrows, Pamela K.; Farmer, Diana; Walsh, William; Johnson, Mark P.; Rand, Larry; Tolivaisa, Susan; D’Alton, Mary E.; Adzick, N. Scott

2016-01-01

Object The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit. Methods The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery. Results Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 [95% CI 0.22–0.66]). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size ≥ 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hindbrain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome. Conclusions Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group. PMID:26369371

Decompressive craniectomy and CSF disorders in children.

PubMed

Manfiotto, Marie; Mottolese, Carmine; Szathmari, Alexandru; Beuriat, Pierre-Aurelien; Klein, Olivier; Vinchon, Matthieu; Gimbert, Edouard; Roujeau, Thomas; Scavarda, Didier; Zerah, Michel; Di Rocco, Federico

2017-10-01

Decompressive craniectomy (DC) is a lifesaving procedure but is associated to several post-operative complications, namely cerebrospinal fluid (CSF) dynamics impairment. The aim of this multicentric study was to evaluate the incidence of such CSF alterations after DC and review their impact on the overall outcome. We performed a retrospective multicentric study to analyze the CSF disorders occurring in children aged from 0 to 17 years who had undergone a DC for traumatic brain injury (TBI) in the major Departments of Pediatric Neurosurgery of France between January 2006 and August 2016. Out of 150 children, ranging in age between 7 months and 17 years, mean 10.75 years, who underwent a DC for TBI in 10 French pediatric neurosurgical centers. Sixteen (6 males, 10 females) (10.67%) developed CSF disorders following the surgical procedure and required an extrathecal CSF shunting. External ventricular drainage increased the risk of further complications, especially cranioplasty infection (p = 0.008). CSF disorders affect a minority of children after DC for TBI. They may develop early after the DC but they may develop several months after the cranioplasty (8 months), consequently indicating the necessity of clinical and radiological close follow-up after discharge from the neurosurgical unit. External ventricular drainage and permanent CSF shunt placement increase significantly the risk of cranioplasty infection.

Intracranial cerebrospinal fluid distribution and its postoperative changes in normal pressure hydrocephalus.

PubMed

Tsunoda, A; Mitsuoka, H; Bandai, H; Arai, H; Sato, K; Makita, J

2001-01-01

This study was conducted to investigate the usefulness of intracranial cerebrospinal fluid (CSF) volume measurement using MR-based methods in the management of patients with normal pressure hydrocephalus (NPH). The study group comprised 19 patients with NPH who showed a favorable outcome after ventricular shunting, 15 normal volunteers (NV), and 15 patients with cerebrovascular disease (CVD). A 3D-fast asymmetric spin echo MR imaging sequence and the region-growing method were used to extract the CSF space from MR images. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured and the VV/ICV ratio was calculated in each case. In NPH patients, the CSF volume was measured again after shunting. The mean VV and VV/ICV ratio in the NPH group (91.1 mL and 45.2%, respectively) were significantly (p < 0.01) higher than those in the NV group (26.5 mL and 13.7%) and in the CVD group (44.5 mL and 17.8%). On the other hand, mean ICV values were not significantly different among the three groups. The VV was markedly decreased postoperatively (mean -40.7%), whereas the ICV was unchanged, resulting in a marked reduction in the VV/ICV ratio (mean -39.3%). These results suggest that patients with NPH have a unique intracranial CSF distribution, with an enlarged VV and a slightly increased ICV, resulting in a high VV/ICV ratio. Shunting led to dramatic improvement in our patients. It is likely that CSF measurement can provide valuable information in the management of patients with NPH.

Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

PubMed Central

Tullberg, Mats; Blennow, Kaj; Månsson, Jan-Eric; Fredman, Pam; Tisell, Magnus; Wikkelsö, Carsten

2008-01-01

Background The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement. Methods We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18) before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery. Results Preoperatively, the only pathological findings were elevated neurofilament protein (NFL), significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH. Conclusion We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH. PMID:18439296

Changes of cerebrospinal fluid protein concentrations and gait patterns in geriatric normal pressure hydrocephalus patients after ventriculoperitoneal shunting surgery.

PubMed

Chen, Carl P C; Huang, Yin-Cheng; Chang, Chen-Nen; Chen, Jean-Lon; Hsu, Chih-Chin; Lin, Wan-Ying

2018-06-01

Normal pressure hydrocephalus (NPH) was the first type of dementia ever described that can be treated using ventriculoperitoneal shunting surgery. Three typical clinical symptoms of NPH include gait disturbance, progressive cognitive dysfunction, and urinary incontinence. Although there are articles that have discovered several cerebrospinal fluid (CSF) protein biomarkers associated with NPH; however, studies examining individual and total protein concentrations from the ventricular CSF before and after shunting surgery are lacking. This study used proteomics to calculate the CSF individual and total protein concentrations before, and one week, one month and three months after the shunting surgery. Parameters of cadence, step length, walking speed, and percentages of single- and double-limb support in a gait cycle were measured. Protein concentrations associated with anti-oxidation, aging, and in the prevention of neurotoxic agent production increased by at least 2-folds after the surgery, indicating that the brain may become less susceptible to neurodegeneration. These proteins were alpha-1B-glycoprotein, apolipoproteins A-1 & A-IV, prostaglandin-H2 D-isomerase, alpha-1-antitrypsin, and serotransferrin. In gait analysis, lower cadence, decreased double-limb support, longer step length, and increased single-limb support were observed after the surgery, indicating a more stable walking balance. These changes lasted for a period of at least 3 months. As a result, shunting surgery may be recommended for geriatric patients with confirmed diagnosis of normal pressure hydrocephalus. Copyright © 2018 Elsevier Inc. All rights reserved.

Management of idiopathic normal-pressure hydrocephalus: a multiinstitutional study conducted in Japan.

PubMed

Mori, K

2001-12-01

A cooperative study was undertaken to identify factors that could be used to predict a favorable outcome after extracranial cerebrospinal fluid (CSF) diversion (shunting) in patients with suspected idiopathic normal-pressure hydrocephalus (NPH). Questionnaires concerning patients with suspected idiopathic NPH were sent to 14 members of the Committee for Scientific Research on Intractable Hydrocephalus, sponsored by the Ministry of Health and Welfare of Japan. After the questionnaires were returned, a retrospective analysis of the responses was undertaken. To be included in the study, patients had to be 65 years of age or older and had to have undergone surgery between October 1995 and October 1998. Clinical measures included degrees of gait disturbance, dementia, and urinary incontinence as evaluated before. 3 months after, and 3 years after shunt placement. Diagnostic tests in various combinations included lumbar puncture in which CSF was withdrawn; intracranial pressure monitoring; measurements of CSF outflow resistance, level of serum alpha-1-antichymotrypsin, cerebral arteriovenous differences of oxygen content, and cerebral blood flow; and computerized tomography cisternography. In this study, 120 patients were identified as having idiopathic NPH and these patients underwent placement of shunts. A ventriculoperitoneal shunt with a programmable valve was used in two thirds of the patients. At the end of 3 months (early assessment), there was an 80% overall rate of clinical improvement, which dropped to 73.3% of the 105 patients who could be evaluated at the end of the 3-year study. Of the three variables, gait disturbance was most improved, both at early and late testing periods. Shunt complications occurred in 22 (18.3%) of the patients. Patients suspected of having idiopathic NPH did not form a homogeneous group, making it difficult to select those who would most likely respond to CSF diversion. Of the diagnostic studies, the most reliable result was improvement in clinical symptoms following a lumbar puncture in which CSF was withdrawn. The use of a programmable valve is recommended because it offers advantages in preventing problems of over- and underdrainage.

The Dynamic Gait Index in Evaluating Patients with Normal Pressure Hydrocephalus for Cerebrospinal Fluid Diversion.

PubMed

Chivukula, Srinivas; Tempel, Zachary J; Zwagerman, Nathan T; Newman, W Christopher; Shin, Samuel S; Chen, Ching-Jen; Gardner, Paul A; McDade, Eric M; Ducruet, Andrew F

2015-12-01

Diagnosing normal pressure hydrocephalus (NPH) remains challenging. Most clinical tests currently used to evaluate suspected NPH patients for shunt surgery are invasive, require inpatient admission, and are not without complications. An objective, noninvasive, and low-cost alternative would be ideal. A retrospective review was performed of prospectively collected dynamic gait index (DGI) scores, obtained at baseline and on every day of a 3- to 5-day lumbar cerebrospinal fluid (CSF) drainage trial on patients with suspected NPH at our institution. Between 2003 and 2014, 170 patients were suspected to have primary NPH (166, 97.6%) or secondary NPH (4, 2.4%). Using responsiveness to lumbar CSF drainage and subsequent shunting as the reference standard, we found that a baseline DGI ≥ 7 was found to have significant ability in selecting patients for permanent CSF diverting shunt surgery: sensitivity of 84.2% (95% confidence interval [95% CI]: 75.6%-90.2%), specificity of 80.6% (95% CI 70.0%-88.0%), and diagnostic odds ratio of 22.1 (95% CI 9.9-49.3). A baseline DGI ≥ 7 appears to provide an objective, low-cost, noninvasive measure to select patients with suspected NPH for a positive response to CSF diversion with high sensitivity, specificity and diagnostic odds ratio. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic ("normal pressure") hydrocephalus in childhood and adolescence. A review of 16 cases and reappraisal of the syndrome.

PubMed

Bret, P; Chazal, J

1995-12-01

"Normal pressure" hydrocephalus (NPH) is generally considered to be a disorder of the adult and geriatric population. Only a few reports have described the possible occurrence of this condition in children. A series of 16 patients aged less than 20 years forms the basis of the present report. Among these 16 patients, 11 had a clearly identified etiologic factor and 7 had had a shunt previously implanted. The majority of patients exhibited at least two elements of the adult's triad of psychomotor retardation (14 cases) and/or psychotic-like symptoms (4 cases), gait anomalies (8 cases), and sphincter disturbances (3 cases). Six patients had their intracranial pressure (ICP) monitored. ICP values were estimated to be within the normal limits for age. All the 16 patients underwent shunting or shunt revision. Surgical results were as follows (mean follow-up 20 +/- 17.2 months): a good response to shunting was obtained in 12 cases ("cured": 5, improved: 7), while the other 4 patients failed to improve. It seems likely that associated parenchymal disorders have played a major role in therapeutic failures. In children showing ventricular dilation on computed tomographic (CT) analysis and a clinical picture of subtle psychomotor deterioration, it may be difficult to distinguish an active disorder of the CSF dynamics from "arrested hydrocephalus." Since intracranial manometry cannot be undertaken as a routine procedure, less invasive methods such as cerebrospinal fluid (CSF) tap test, psychometric, or urodynamic tests deserve special attention as reliable predictors of outcome after shunting. Because most patients undergo shunting without prior assessment of their CSF pressure, the term "chronic hydrocephalus" is proposed as an alternative designation to "NPH," since there is little argument for maintaining an instrumentally based definition of the syndrome.

Normal pressure hydrocephalus: long-term outcome after shunt surgery.

PubMed

Pujari, S; Kharkar, S; Metellus, P; Shuck, J; Williams, M A; Rigamonti, D

2008-11-01

Little is known about the long-term clinical course and management of patients with normal pressure hydrocephalus (NPH) treated by cerebrospinal fluid (CSF) shunting. We retrospectively reviewed records of 55 patients diagnosed with idiopathic NPH (INPH) and treated with CSF shunts, all of whom were followed for more than 3 years after the original shunt surgery. At each annual follow-up visit, the patient was assessed by Folstein Mini Mental State Examination, detailed clinical evaluation of gait and assessment of headache, cognition, gait or urination, as assessed by the patient and relatives. The mean duration of follow-up was 5.9+/-2.5 years. There was an overall sustained improvement among all symptoms. Gait showed the highest maintenance of improvement over baseline (83% at 3 years and 87% at the last analysed follow-up of 7 years), cognition showed intermediary improvement (84% and 86%, respectively), and urinary incontinence showed the least improvement (84% and 80%, respectively). Fifty-three percent of patients required shunt revisions. Indications for revision included shunt malfunction (87%), infection (10%) and change of shunt configuration (3%). Overall, 74% revisions resulted in clinical improvement. Clinical improvement of patients with NPH can be sustained for 5-7 years in some patients with NPH, even if shunt revision surgery is needed multiple times. With earlier diagnosis and treatment of NPH and the increasing lifespan of the ageing population, the need for long-term follow-up after shunt surgery for NPH may be greater than it was in the past. Monitoring, identification and treatment of shunt obstruction is a key management principle.

Our initial experience with ventriculo-epiplooic shunt in treatment of hydrocephalus in two centers.

PubMed

Grigorean, Valentin Titus; Sandu, Aurelia Mihaela; Popescu, Mihai; Florian, Ioan Stefan; Lupascu, Cristian Dumitru; Ursulescu, Corina Lupascu

Hydrocephalus represents impairment in cerebrospinal fluid (CSF) dynamics. If the treatment of hydrocephalus is considered difficult, the repeated revisions of ventriculo-peritoneal (VP) shunts are even more challenging. The aim of this article is to evaluate the efficiency of ventriculo-epiplooic (VEp) shunt as a feasible alternative in hydrocephalic patients. A technical modification regarding the insertion of peritoneal catheter was imagined: midline laparotomy 8-10cm long was performed in order to open the peritoneal cavity; the great omentum was dissected between its two layers; we placed the distal end of the catheter between the two epiplooic layers; a fenestration of 4cm in diameter into the visceral layer was also performed. A retrospective study of medical records of 15 consecutive patients with hydrocephalus treated with VEp shunt is also presented. Between 2008 and 2014 we performed VEp shunt in 15 patients: 5 with congenital hydrocephalus, 8 with secondary hydrocephalus and 2 with normal pressure hydrocephalus. There were 7 men and 8 women. VEp shunt was performed in 13 patients with multiple distal shunt failures and in 2 patients, with history of abdominal surgery, as de novo extracranial drainage procedure. The outcome was favorable in all cases, with no significant postoperative complications. VEp shunt is a new, safe and efficient surgical technique for the treatment of hydrocephalus. VEp shunt is indicated in patients with history of recurrent distal shunt failures, and in patients with history of open abdominal surgery and high risk for developing abdominal complications. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Intramedullary placement of ventricular shunts: a review of using bone as a distal cerebrospinal absorption site in treating hydrocephalus.

PubMed

Kassem, Mohammad W; Chern, Joshua; Loukas, Marios; Tubbs, R Shane

2017-12-01

Intraosseous (IO) vascular access has been used since the Second World War and is warranted when there is an emergency and/or urgent need to replenish the vascular pool. Despite long-term and satisfactory results from delivering large quantities of intravenous fluid via the medullary space of bone, use of this space for a distant receptacle for cerebrospinal fluid (CSF) diversion has seldom been considered. The current paper reviews the literature regarding the bony medullary space as a receptacle for intravenous fluid and CSF. Previous authors have demonstrated the potential of the diploic space of the calvaria for CSF shunting. Pugh and colleagues tested the ability of the cranium to receive and absorb a small amount of tracer fluid. The literature suggests that intraosseous placement of ventricular diversionary shunts is an alternative to more traditional sites such as the pleural cavity and peritoneum. When these latter locations are not available or are contraindicated, placement in the medullary space of bone is another option available to the surgeon.

Ten years of clinical experience in the use of fixed-pressure versus programmable valves: a retrospective study of 159 patients.

PubMed

Mpakopoulou, Maria; Brotis, Alexandros G; Gatos, Haralampos; Paterakis, Konstantinos; Fountas, Kostas N

2012-01-01

The aim of this study was to present our 10-year experience with the use of fixed-pressure and programmable valves in the treatment of adult patients requiring cerebrospinal fluid (CSF) diversion. Patients (n = 159; 89 male and 70 female) suffering from hydrocephalus of various causes underwent CSF shunt implantation. Forty fixed-pressure and 119 programmable valves were initially implanted. The observed revision rate was 40% in patients with fixed-pressure valves. In 20% of these patients, a revision due to valve mechanism malfunction was undertaken, and the initial valve was replaced with a programmable one. The revision rate in the adjustable-pressure valve subgroup was 20%. The infection rate for the fixed-pressure and programmable valve subgroups were 3%, and 1.7%, respectively. Similarly, subdural fluid collections were noticed in 17% and 4% of patients with fixed-pressure valves and programmable valves, respectively. The revision and over-drainage rates were significantly lower when using programmable valves, and thus, this type of valve is preferred whenever CSF has to be diverted.

Comparison between the lumbar infusion and CSF tap tests to predict outcome after shunt surgery in suspected normal pressure hydrocephalus

PubMed Central

Kahlon, B; Sundbarg, G; Rehncrona, S

2002-01-01

Objective: To compare the lumbar infusion test and the cerebrospinal fluid (CSF) tap test for predicting the outcome of shunt surgery in patients with suspected normal pressure hydrocephalus. Methods: 68 patients with suspected normal pressure hydrocephalus were studied. The absence of preceding history indicated idiopathic disease in 75% of these. All patients were assessed twice with walking and psychometric tests before lumbar infusion test and tap test assessments. The lumbar infusion test was done using a constant infusion rate (0.80 ml/min) and regarded as positive if the steady state CSF plateau pressure reached levels of > 22 mm Hg (resistance to outflow > 14 mm Hg/ml/min). The tap test was regarded as positive if two or more of four different test items improved after CSF removal. As the variability in baseline test results was large, the better of two evaluations was used in comparisons with the results after CSF removal, as well as to evaluate the outcome after shunt surgery. Only patients with a positive lumbar infusion test or a positive tap test had surgery. Results: The results of the CSF tap test and the lumbar infusion test agreed in only 45% of the patients. Of the total cohort, 47 (69%) had positive test results and were operated on; 45 (96%) of these reported subjective improvement, and postoperative assessments verified the improvements in 38 (81%). Improvements were highly significant in walking, memory, and reaction time tests (p < 0.001). Most of the patients improved by surgery (84%) were selected by a positive lumbar infusion test, and only 42% by a positive tap test. Positive predictive values were 80% for lumbar infusion test and 94% for tap test. The false negative predictions in the operated group were much higher (58%) with the tap test than with the lumbar infusion test (16%). Conclusions: Both the lumbar infusion test and the tap test can predict a positive outcome of shunt operations in unselected patients with suspected normal pressure hydrocephalus. The two tests are complementary and should be used together for optimal patient selection. PMID:12438477

Comparison between the lumbar infusion and CSF tap tests to predict outcome after shunt surgery in suspected normal pressure hydrocephalus.

PubMed

Kahlon, B; Sundbärg, G; Rehncrona, S

2002-12-01

To compare the lumbar infusion test and the cerebrospinal fluid (CSF) tap test for predicting the outcome of shunt surgery in patients with suspected normal pressure hydrocephalus. 68 patients with suspected normal pressure hydrocephalus were studied. The absence of preceding history indicated idiopathic disease in 75% of these. All patients were assessed twice with walking and psychometric tests before lumbar infusion test and tap test assessments. The lumbar infusion test was done using a constant infusion rate (0.80 ml/min) and regarded as positive if the steady state CSF plateau pressure reached levels of > 22 mm Hg (resistance to outflow > 14 mm Hg/ml/min). The tap test was regarded as positive if two or more of four different test items improved after CSF removal. As the variability in baseline test results was large, the better of two evaluations was used in comparisons with the results after CSF removal, as well as to evaluate the outcome after shunt surgery. Only patients with a positive lumbar infusion test or a positive tap test had surgery. The results of the CSF tap test and the lumbar infusion test agreed in only 45% of the patients. Of the total cohort, 47 (69%) had positive test results and were operated on; 45 (96%) of these reported subjective improvement, and postoperative assessments verified the improvements in 38 (81%). Improvements were highly significant in walking, memory, and reaction time tests (p < 0.001). Most of the patients improved by surgery (84%) were selected by a positive lumbar infusion test, and only 42% by a positive tap test. Positive predictive values were 80% for lumbar infusion test and 94% for tap test. The false negative predictions in the operated group were much higher (58%) with the tap test than with the lumbar infusion test (16%). Both the lumbar infusion test and the tap test can predict a positive outcome of shunt operations in unselected patients with suspected normal pressure hydrocephalus. The two tests are complementary and should be used together for optimal patient selection.

Idiopathic normal pressure hydrocephalus: the CSF tap-test may predict the clinical response to shunting.

PubMed

Sand, T; Bovim, G; Grimse, R; Myhr, G; Helde, G; Cappelen, J

1994-05-01

A follow-up study was performed in nine patients with idiopathic normal pressure hydrocephalus (NPH) 37 months (mean) after shunting and 10 non-operated controls with comparable degrees of ventricular enlargement, gait disorder, and dementia. Five operated patients vs. no controls reported sustained general improvement (p < 0.02). Objectively improved gait at follow-up (compared with preoperative status) was found in five of the six tested NPH-patients vs. none of the controls (p < 0.005). Improved gait and/or psychometric function was found in four of six NPH vs. none of eight control patients (p < 0.02) after drainage of 40 ml cerebrospinal fluid (CSF tap-test). Improved gait during the CSF tap-test predicted continued improvement at follow-up. Temporal horn size was the only radiological variable which showed a (moderate) positive correlation with resistance to CSF absorption and rate of pressure increase. The size of the third ventricle diminished in parallel with clinical improvement.

Syringomyelia caused by an arachnoid web in a patient with shunted Dandy-Walker malformation.

PubMed

Lee, Hee Chang; Choi, Jung Won; Lee, Ji Yeoun; Phi, Ji Hoon; Kim, Seung-Ki; Cho, Byung-Kyu; Wang, Kyu-Chang

2017-04-01

Dandy-Walker malformation (DWM) is a congenital brain anomaly characterized by dysgenesis of the cerebellar vermis and the presence of a posterior fossa cyst. The association of syringomyelia with DWM is extremely rare. A 10-year-old patient who was diagnosed with DWM in infancy presented with progressive scoliosis and fecal incontinence. He had been treated with cystoventriculoperitoneal shunting with a Y-connection during infancy, which was followed by a revision 6 years later. During the revision surgery, intraventricular bleeding occurred and was managed conservatively. Imaging studies for the current visit revealed syringomyelia along the cervicothoracic spinal cord and a membranous structure around the cervicomedullary junction. Phase-contrast cine magnetic resonance imaging (MRI) revealed disturbed cerebrospinal fluid (CSF) flow across the membrane. We excised the arachnoid web that was tethering the brainstem and blocking CSF flow. Postoperatively, the patient experienced symptom relief, and the follow-up imaging study demonstrated a dramatic decrease in the size of the syringomyelia. We suggest that syrinx formation in this patient was possibly caused by disturbed CSF flow and tethering of the brainstem. We experienced an unusual case of DWM with syringomyelia which was caused by an arachnoid web blocking CSF flow and tethering the brainstem. The arachnoid web seems to be formed by previous bleeding which occurred at the time of shunt revision. After excision of the arachnoid web, the patient showed good outcome.

Gait and Balance Measures Can Identify Change From a Cerebrospinal Fluid Tap Test in Idiopathic Normal Pressure Hydrocephalus.

PubMed

Gallagher, Ryan; Marquez, Jodie; Osmotherly, Peter

2018-04-25

To identify in patients with idiopathic normal pressure hydrocephalus (iNPH) undergoing a cerebrospinal fluid (CSF) tap test (TT) for consideration of a ventricular peritoneal (VP) shunt: (1) gait and balance measures, which identify symptom change; (2) differences present between pre- and post-CSF TT scores between patients classified as responders and nonresponder; (3) ability of patients with iNPH to accurately quantify change in their gait and balance symptoms from a CSF TT. Prospective observational study. Post-CSF TT assessment was completed 2-4 hours post. Tertiary referral neurological and neurosurgical hospital. Patients (N=74) with iNPH receiving a 30 mL CSF TT for consideration of a VP shunt. Patients underwent a battery of gait and balance measures pre- and post-CSF TT and indicated their perceived change on a global rating of change (GRC). Patients deemed to improve and offered VP shunt insertion by a neurologist or neurosurgeon were labeled responders. Performance oriented mobility assessment (Tinetti), Berg Balance Scale (BBS), timed Up and Go (TUG), 10-meter walk test (10MWT), GRC. Forty patients were classified responders, 34 nonresponders. Significant differences were identified for responders: Tinetti (3.88 points), TUG (3.98 seconds), 10MWT (0.08 m/sec), and BBS (5.29 points). Significant differences were found for nonresponders for the Tinetti (0.91 points) and BBS (2.06 points). Change scores for responders and nonresponders were significantly different for all tests between responders and nonresponders. GRC scores for gait (+2 for responders, 0 for nonresponders) and balance (+2.5 for responders, 0 for nonresponders) were both significantly different. The Tinetti, BBS, and TUG can identify change in patients undergoing a CSF TT for iNPH. Patients appear to be able to accurately identify if change has occurred. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

2014-03-01

Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

Rate of shunt revision as a function of age in patients with shunted hydrocephalus due to myelomeningocele.

PubMed

Dupepe, Esther B; Hopson, Betsy; Johnston, James M; Rozzelle, Curtis J; Jerry Oakes, W; Blount, Jeffrey P; Rocque, Brandon G

2016-11-01

OBJECTIVE It is generally accepted that cerebrospinal fluid shunts fail most frequently in the first years of life. The purpose of this study was to describe the risk of shunt failure for a given patient age in a well-defined cohort with shunted hydrocephalus due to myelomeningocele (MMC). METHODS The authors analyzed data from their institutional spina bifida research database including all patients with MMC and shunted hydrocephalus. For the entire population, the number of shunt revisions in each year of life was determined. Then the number of patients at risk for shunt revision during each year of life was calculated, thus enabling them to calculate the rate of shunt revision per patient in each year of life. In this way, the timing of all shunt revision operations for the entire clinic population and the likelihood of having a shunt revision during each year of life were calculated. RESULTS A total of 655 patients were enrolled in the spina bifida research database, 519 of whom had a diagnosis of MMC and whose mean age was 17.48 ± 11.7 years (median 16 years, range 0-63 years). Four hundred seventeen patients had had a CSF shunt for the treatment of hydrocephalus and thus are included in this analysis. There were 94 shunt revisions in the 1st year of life, which represents a rate of 0.23 revisions per patient in that year. The rate of shunt revision per patient-year initially decreased as age increased, except for an increase in revision frequency in the early teen years. Shunt revisions continued to occur as late as 43 years of age. CONCLUSIONS These data substantiate the idea that shunt revision surgeries in patients with MMC are most common in the 1st year of life and decrease thereafter, except for an increase in the early teen years. A persistent risk of shunt failure was observed well into adult life. These findings underscore the importance of routine follow-up of all MMC patients with shunted hydrocephalus and will aid in counseling patients and families.

Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

PubMed Central

Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

2014-01-01

Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (Aβ) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau), non-AD-related Aβ isoforms (Aβ38, Aβ40), sAPP isoforms (sAPPα, sAPPβ), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPPα were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = −0.295, p = 0.003) and lumbar (r = −0.356, p = 0.01) samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD. PMID:24638077

Clinical outcomes of temporary shunting for infants with cerebral pseudomeningocele.

PubMed

Mattei, Tobias A; Sambhara, Deepak; Bond, Brandon J; Lin, Julian

2014-02-01

Although in the case of subdural collections temporary shunting has been suggested as a viable alternative for definitive drainage of the accumulated fluid until restoration of the normal CSF dynamics, there is no agreement on the best management strategy for pseudomeningocele. The authors performed a retrospective chart review in order to evaluate the clinical outcomes of infants temporarily shunted for pseudomeningocele without encephalocele at our institution (The University of Illinois at Peoria/Illinois Neurological Institute) in the period from 2004 to 2012. The epidemiological characteristics, clinical management, and final outcomes of such subpopulation were compared with a control group which received temporary shunting for subdural hematomas (SDH) during the same period. Four patients (100% male) ranging in age from 8.9 to 27.1 months (mean = 13.88) with pseudomeningocele and 17 patients (64.7% male) ranging in age from 1.9 to 11.8 months (mean = 4.15) with SDH were identified. Although the initial management included sequential percutaneous subdural tapping in 82% of the patients, all children ultimately failed such strategy, requiring either subdural-peritoneal (81% of the cases) or subgaleal-peritoneal (19% of the cases) shunting. The mean implant duration was 201 days for the pseudomeningocele group and 384 days for the SDH one. Mean post-shunt hospitalization was 2 days for patients with pseudomeningocele and 4 days for patients with SDH. There was no statistical difference in terms of complications, length of hospitalization post-shunting, or clinical outcomes between the patients with pseudomeningocele and those with SDH. Temporary shunting of infants with pseudo-meningocele constitutes a viable therapeutic alternative with favorable clinical outcomes and a low risk of shunt dependency similar to those of children with SDH.

Implantable Systems for Continuous Liquorpheresis and CSF Replacement

PubMed Central

2017-01-01

Liquorpheresis (cerebrospinal fluid filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators, or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. Continuous or intermittent cerebrospinal fluid (CSF) replacement may be an alternative approach not explored thus far. Here, we review previous experiences in the use of liquorpheresis in autoimmune and degenerative neurological diseases. Then we describe previous technical reports  and provide some new innovations in order to design bidirectional CSF shunting systems that can be complemented either with a deposit of artificial CSF or with a filter of CSF, allowing CSF replacement or liquorpheresis respectively. Both options would lead to mechanical dilution of the patient’s CSF. PMID:28413734

The pathophysiology of chronic noncommunicating hydrocephalus: lessons from continuous intracranial pressure monitoring and ventricular infusion testing.

PubMed

Eide, Per Kristian

2017-08-11

OBJECTIVE The pathophysiology of chronic noncommunicating hydrocephalus (ncHC) is poorly understood. This present study explored whether lessons about the pathophysiology of this clinical entity might be retrieved from results of overnight monitoring of pulsatile and static intracranial pressure (ICP) and ventricular infusion testing. METHODS The study cohort included adult patients (> 20 years of age) with chronic ncHC due to aqueductal stenosis in whom symptoms had lasted a minimum of 6 months. A reference cohort consisted of age- and sex-matched patients managed for communicating HC (cHC). Information about symptoms and clinical improvement following surgery was retrieved from a quality register, and results of overnight ICP recordings and ventricular infusion testing were retrieved from the hospital ICP database. RESULTS The cohort with ncHC consisted of 61 patients of whom 6 (10%) were managed conservatively, 34 (56%) by endoscopic third ventriculostomy (ETV), and 21 (34%) using ETV and subsequent shunt surgery. In patients responding to surgery, pulsatile ICP (mean ICP wave amplitude) was significantly increased to a similar magnitude in patients with ncHC and the reference cohort (cHC). Furthermore, intracranial compliance (ICC) was reduced in clinical responders. The results of ventricular infusion testing provided evidence that patients responding to ETV have impaired ventricular CSF absorption, while those requiring shunt placement after ETV present with impaired CSF absorption both in the intraventricular and extraventricular compartments. CONCLUSIONS The study may provide some lessons about the pathophysiology of chronic ncHC. First, increased pulsatile ICP and impaired ICC characterize patients with chronic ncHC who respond clinically to CSF diversion surgery, even though static ICP is not increased. Second, in patients responding clinically to ETV, impaired ventricular CSF absorption may be a key factor. Patients requiring shunt placement for clinical response appear to have both intraventricular and extraventricular CSF absorption failure. A subgroup of patients with ncHC due to aqueductal stenosis has normal ventricular CSF absorption and normal ICC and may not be in need of surgical CSF diversion.

Selection of patients with idiopathic normal-pressure hydrocephalus for shunt placement: a single-institution experience.

PubMed

Anile, Carmelo; De Bonis, Pasquale; Albanese, Alessio; Di Chirico, Alessandro; Mangiola, Annunziato; Petrella, Gianpaolo; Santini, Pietro

2010-07-01

The ability to predict outcome after shunt placement in patients with idiopathic normal-pressure hydrocephalus (NPH) represents a challenge. To date, no single diagnostic tool or combination of tools has proved capable of reliably predicting whether the condition of a patient with suspected NPH will improve after a shunting procedure. In this paper, the authors report their experience with 120 patients with the goal of identifying CSF hydrodynamics criteria capable of selecting patients with idiopathic NPH. Specifically, they focused on the comparison between CSF-outflow resistance (R-out) and intracranial elastance (IE). Between January 1977 and December 2005, 120 patients in whom idiopathic NPH had been diagnosed (on the basis of clinical findings and imaging) underwent CSF hydrodynamics evaluation based on an intraventricular infusion test. Ninety-six patients underwent CSF shunt placement: 32 between 1977 and 1989 (Group I) on the basis of purely clinical and radiological criteria; 44 between 1990 and 2002 (Group II) on the basis of the same criteria as Group I and because they had an IE slope > 0.25; and 20 between 2003 and 2005 (Group III) on the basis of the same criteria as Group II but with an IE slope > or = 0.30. Outcomes were evaluated by means of both Stein-Langfitt and Larsson scores. Patients' conditions were considered improved when there was a stable decrease (at 6- and 12-month follow-up) of at least 1 point in the Stein-Langfitt score and 2 points in the Larsson score. Group I: while no statistically significant difference in mean R-out value between improved and unimproved cases was observed, a clear-cut IE slope value of 0.25 differentiated very sharply between unimproved and improved cases. Group II: R-out values in the 2 unimproved cases were 20 and 47 mm Hg/ml/min, respectively. The mean IE slope in the improved cases was 0.56 (range 0.30-1.4), while the IE slopes in the 2 unimproved cases were 0.26 and 0.27. Group III: the mean IE slope was 0.51 (range 0.31-0.7). The conditions of all patients improved after shunting. A significant reduction of the Evans ratio was observed in 34 (40.5%) of the 84 improved cases and in none of the unimproved cases. Our strategy based on the analysis of CSF pulse pressure parameters seems to have a great accuracy in predicting surgical outcome in clinical practice.

Hydrocephalus in Dandy-Walker malformation.

PubMed

Spennato, Pietro; Mirone, Giuseppe; Nastro, Anna; Buonocore, Maria Consiglio; Ruggiero, Claudio; Trischitta, Vincenzo; Aliberti, Ferdinando; Cinalli, Giuseppe

2011-10-01

Even if the first description of Dandy-Walker dates back 1887, difficulty in the establishment of correct diagnosis, especially concerning differential diagnosis with other types of posterior fossa CSF collection, still persists. Further confusion is added by the inclusion, in some classification, of different malformations with different prognosis and therapeutic strategy under the same label of "Dandy-Walker". An extensive literature review concerning embryologic, etiologic, pathogenetic, clinical and neuroradiological aspects has been performed. Therapeutic options, prognosis and intellectual outcome are also reviewed. The correct interpretation of the modern neuroradiologic techniques, including CSF flow MR imaging, may help in identifying a "real" Dandy-Walker malformation. Among therapeutical strategies, single shunting (ventriculo-peritoneal or cyst-peritoneal shunts) appears effective in the control of both ventricle and cyst size. Endoscopic third ventriculostomy may be considered an acceptable alternative, especially in older children, with the aim to reduce the shunt-related problems. Prognosis and intellectual outcome mostly depend on the presence of associated malformations, the degree of vermian malformation and the adequate control of hydrocephalus.

Idiopathic normal pressure hydrocephalus: analysis of factors related to cerebrospinal fluid dynamics determining functional prognosis.

PubMed

Bárcena, A; Mestre, C; Cañizal, J M; Rivero, B; Lobato, R D

1997-01-01

This investigation has been undertaken to analyze the findings with both the cerebrospinal fluid (CSF) pressure (Pcsf) and CSF pulse pressure (PP) in order to predict the outcome of patients with the syndrome of idiopathic normal pressure hydrocephalus (NPH). Accordingly, a prospective clinical study was planned in which two groups of patients with NPH, having analogous prevalence of several matched clinical and radiological parameters, were separated on the basis of their positive or negative response to shunting. Both the resting Pcsf and CSF PP profiles were compared in these two groups, and between them and normal controls. CSF PP amplitude and CSF PP latency correlated directly in conditions associated with either normal or high compliance (controls and patients with Alzheimer-like disorders), whereas this correlation was inverse in states of low compliance (NPH). On the other hand, shunt-responders showed a resting Pcsf significantly higher than both non-responders and controls. The following conclusions were obtained: 1) CSF PP is a high-amplitude and relative low-latency wave in NPH when compared with controls: 2) CSF PP amplitude and latency correlate directly in normal subjects and in those with primary cerebral atrophy; 3) a non-reversible stage of NPH could be conceived in contradistinction to the reversible one, in both of which an inverse correlation between the amplitude and the latency takes place, the main difference between them being the resting Pcsf, which is significantly lower in the former than in the latter, depending on the degree of atrophic changes developed.

Negative-pressure and low-pressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base.

PubMed

Filippidis, Aristotelis S; Kalani, M Yashar S; Nakaji, Peter; Rekate, Harold L

2011-11-01

Negative-pressure and low-pressure hydrocephalus are rare clinical entities that are frequently misdiagnosed. They are characterized by recurrent episodes of shunt failure because the intracranial pressure is lower than the opening pressure of the valve. In this report the authors discuss iatrogenic CSF leaks as a cause of low- or negative-pressure hydrocephalus after approaches to the cranial base. The authors retrospectively reviewed cases of low-pressure or negative-pressure hydrocephalus presenting after cranial approaches complicated with a CSF leak at their institution. Three patients were identified. Symptoms of high intracranial pressure and ventriculomegaly were present, although the measured pressures were low or negative. A blocked communication between the ventricles and the subarachnoid space was documented in 2 of the cases and presumed in the third. Shunt revisions failed repeatedly. In all cases, temporary clinical and radiographic improvement resulted from external ventricular drainage at subatmospheric pressures. The CSF leaks were sealed and CSF communication was reestablished operatively. In 1 case, neck wrapping was used with temporary success. Negative-pressure or low-pressure hydrocephalus associated with CSF leaks, especially after cranial base approaches, is difficult to treat. The solution often requires the utilization of subatmospheric external ventricular drains to establish a lower ventricular drainage pressure than the drainage pressure created in the subarachnoid space, where the pressure is artificially lowered by the CSF leak. Treatment involves correction of the CSF leak, neck wrapping to increase brain turgor and allow the pressure in the ventricles to rise to the level of the opening pressure of the valve, and reestablishing the CSF route.

Improvised external ventricular drain in neurosurgery: A Nigerian tertiary hospital experience.

PubMed

Ojo, O A; Asha, M A; Bankole, O B; Kanu, O O

2015-01-01

The most common type of hydrocephalus in developing countries is post infective hydrocephalus. Infected cerebrospinal fluid (CSF) however cannot be shunted for the reason that it will block the chamber of the ventriculo-peritoneal (VP) shunt due to its high protein content. In centers where standard external ventricular drain (EVD) sets are not available, improvised feeding tube can be used. The main focus of this study is to encourage the use of improvised feeding tube catheters for EVD when standard sets are not available to improve patients' survival. This was a prospective study. Consecutive patients with hydrocephalus that cannot be shunted immediately for high chances of shunt failure or signs of increasing intracranial pressure were recruited into the study. Other inclusion criteria were preoperative brain tumor with possibility of blocked CSF pathway and massive intraventricular hemorrhage necessitating ventricular drainage as a salvage procedure. Standard EVD set is not readily available and too expensive for most of the parents to afford. Improvised feeding tube is used to drain/divert CSF using the standard documented procedure for EVD insertion. Outcome is measured and recorded. A total of 28 patients were recruited into the study over a time frame of 2 years. There were 19 (67.9%) male and 9 (32.1%) females with a ratio of about 2:1. Age ranges varied from as low as 7 days to 66 years. The median age of the study sample was 6.5 months while the mean was 173.8 months. Duration of EVD varied from 2 days to 11 days with a median of 7 while the average was 6 days. Eventual outcome following the procedure of EVD showed that 19 (67.9%) survived and were discharged either to go home or to have VP shunt afterwards while 8 (28.6%) of the patients died. External ventricular drain can and should be done when it is necessary. Potential mortalities could be reduced by the improvised drainage using a standard feeding tube as described.

Reduction of ventricular size after shunting for normal pressure hydrocephalus related to CSF dynamics before shunting.

PubMed Central

Tans, J T; Poortvliet, D C

1988-01-01

Reduction of ventricular size was determined by repeated computed tomography in 30 adult patients shunted for normal pressure hydrocephalus (NPH) and related to the pressure-volume index (PVI) and resistance to outflow of cerebrospinal fluid (Rcsf) measured before shunting. Rapid and marked reduction of ventricular size (n = 10) was associated with a significantly lower PVI than slow and moderate to marked (n = 13) or minimal to mild reduction (n = 7). Otherwise no relationship could be found between the reduction of ventricular size and PVI or Rcsf. It is concluded that both rate and magnitude of reduction of ventricular size after shunting for NPH are extremely variable. High brain elasticity seems to be the best predictor of rapid and marked reduction. PMID:3379425

Brain CT scan indexes in the normal pressure hydrocephalus: predictive value in the outcome of patients and correlation to the clinical symptoms.

PubMed

Chatzidakis, Emmanuel M; Barlas, George; Condilis, Nicolas; Bouramas, Dimos; Anagnostopoulos, Demetrios; Volikas, Zacharias; Simopoulos, Konstantinos

2008-01-01

The aim of this study is to find out the correlation of the ventricular size of the brain, as it is estimated using brain computed tomography (CT) scan indexes in patients with normal pressure hydrocephalus (NPH), to: a) the clinical symptoms, and b) the results of cerebrospinal fluid (CSF) shunting procedures. We looked for any predictive value in the estimation of brain CT scan indexes, in patients as above, in whom a shunt is going to be placed. It is well known that it is very difficult to decide who is going to improve after shunting. We studied 40 cases of patients with the diagnosis "NPH" in whom the ventricular shunts were placed. Every symptom (motor disturbance, deficit of memory, incontinence) was separately evaluated preoperatively. The outcome of shunting was also evaluated and the patients were graded. The following CT scan indexes were estimated from the preoperative CT scans of the brain in every case: the ventricle-brain ratio (VBR), the bi-caudate and bi-frontal ratios, the third ventricle-Sylvian fissure (3V-SF) ratio, and the four largest cortical gyri. The method we have used for statistics is "one way analysis of variance", correlating the CT scan indexes to the symptoms of the patients preoperatively, and the outcome of them postoperatively. The main conclusion is that the size of the lateral ventricles of the brain preoperatively is not correlated to the outcome after CSF shunting surgery, but it is correlated to the symptoms of NPH preoperatively.

The Utility and Benefits of External Lumbar CSF Drainage after Endovascular Coiling on Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Kwon, Ou Young; Kim, Young Jin; Cho, Chun Sung; Lee, Sang Koo; Cho, Maeng Ki

2008-01-01

Objective Cerebral vasospasm still remains a major cause of the morbidity and mortality, despite the developments in treatment of aneurysmal subarachnoid hemorrhage. The authors measured the utility and benefits of external lumbar cerebrospinal fluid (CSF) drainage to prevent the clinical vasospasm and its sequelae after endovascular coiling on aneurysmal subarachnoid hemorrhage in this randomized study. Methods Between January 2004 and March 2006, 280 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Among them, 107 patients met our study criteria. The treatment group consisted of 47 patients who underwent lumbar CSF drainage during vasospasm risk period (about for 14 days after SAH), whereas the control group consisted of 60 patients who received the management according to conventional protocol without lumbar CSF drainage. We created our new modified Fisher grade on the basis of initial brain computed tomography (CT) scan at admission. The authors established five outcome criteria as follows : 1) clinical vasospasm; 2) GOS score at 1-month to 6-month follow-up; 3) shunt procedures for hydrocephalus; 4) the duration of stay in the ICU and total hospital stay; 5) mortality rate. Results The incidence of clinical vasospasm in the lumbar drain group showed 23.4% compared with 63.3% of individuals in the control group. Moreover, the risk of death in the lumbar drain group showed 2.1% compared with 15% of individuals in the control group. Within individual modified Fisher grade, there were similar favorable results. Also, lumbar drain group had twice more patients than the control group in good GOS score of 5. However, there were no statistical significances in mean hospital stay and shunt procedures between the two groups. IVH was an important factor for delayed hydrocephalus regardless of lumbar drain. Conclusion Lumbar CSF drainage remains to play a prominent role to prevent clinical vasospasm and its sequelae after endovascular coiling on aneurysmal subarachnoid hemorrhage. Also, this technique shows favorable effects on numerous neurological outcomes and prognosis. The results of this study warrant clinical trials after endovascular treatment in patients with aneurysmal SAH. PMID:19096633

Normal pressure hydrocephalus: survey on contemporary diagnostic algorithms and therapeutic decision-making in clinical practice.

PubMed

Krauss, J K; Halve, B

2004-04-01

There is no agreement on the best diagnostic criteria for selecting patients with normal pressure hydrocephalus (NPH) for CSF shunting. The primary objective of the present study was to provide a contemporary survey on diagnostic algorithms and therapeutic decision-making in clinical practice. The secondary objective was to estimate the incidence of NPH. Standardized questionnaires with sections on the incidence of NPH and the frequency of shunting, evaluation of clinical symptoms, and signs, diagnostic studies, therapeutic decision-making and operative techniques, postoperative outcome and complications, and the profiles of different centers, were sent to 82 neurosurgical centers in Germany known to participate in the care of patients with NPH. Data were analyzed from 49 of 53 centers which responded to the survey (65%). The estimated annual incidence of NPH was 1.8 cases/100.000 inhabitants. Gait disturbance was defined as the most important sign of NPH (61%). There was a wide variety in the choice of diagnostic tests. Cisternography was performed routinely only in single centers. Diagnostic CSF removal was used with varying frequency by all centers except one, but the amount of CSF removed by lumbar puncture differed markedly between centers. There was poor agreement on criteria for evaluation of continuous intracranial pressure recordings regarding both the amplitude and the relative frequency of B-waves. Both periventricular and deep white matter lesions were present in about 50% of patients being shunted, indicating that vascular comorbidity in NPH patients has gained more acceptance. Programmable shunts were used by more than half of the centers, and newer valve types such as gravitational valves have become more popular. According to the present survey, new diagnostic and therapeutic concepts on NPH have penetrated daily routine to a certain extent. Wide variability, however, still exists among different neurosurgical centers.

Overdrainage after ventriculoperitoneal shunting in a patient with a wide depressed skull bone defect: The effect of atmospheric pressure gradient.

PubMed

Zhou, Lixiang; Yu, Jinlu; Sun, Lichao; Han, Yanwu; Wang, Guangming

2016-01-01

In patients with traumatic brain injury, an effective approach for managing refractory intracranial hypertension is wide decompressive craniectomy. Postoperative hydrocephalus is a frequent complication requiring cerebrospinal fluid (CSF) diversion. A 50-year-old male who underwent decompressive craniectomy after traumatic brain injury. He developed hydrocephalus postoperatively, and accordingly we placed a ventriculoperitoneal shunt. However, an imbalance between the intra- and extra-cranial atmospheric pressures led to overdrainage, and he suffered cognitive disorders and extremity weakness. He remained supine for 5days to avoid the effect of gravity on CSF diversion. After 20days, we performed a cranioplasty using a titanium plate. The postoperative course was uneventful, and the patient achieved satisfactory recovery. The gravitational effect and the atmospheric pressure gradient effect are two factors associated in the ventriculoperitoneal (VP) shunt treatment of hydrocephalus for the patient who had decompressive craniectomy. These effects can be eliminated by supine bed rest and cranioplasty. We herein emphasize the efficacy of VP shunt, supine bed rest and cranioplasty in treating hydrocephalus patients who have undergone craniectomy. A flexible application of these procedures to change the gravitational effect and the atmospheric pressure gradient effect should promote a favorable outcome. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Does CSF outflow resistance predict the response to shunting in patients with normal pressure hydrocephalus?

PubMed

Boon, A J; Tans, J T; Delwel, E J; Egeler-Peerdeman, S M; Hanlo, P W; Wurzer, J A; Avezaat, C J; de Jong, D A; Gooskens, R H; Hermans, J

1998-01-01

The value of the measurements of CSF outflow resistance (Rcsf) relative to predicting outcome after shunting was studied. In a group of 101 patients with mainly idiopathic normal pressure hydrocephalus (NPH) Rcsf was obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified using an NPH scale (NPHS) and disability by the Modified Rankin scale (MRS). Patients were assessed before and at 1, 3, 6, 9 and 12 months after surgery. Outcome measures were differences between the preoperative and last NPHS and MRS scores. Improvement was defined as a change of > or = 15% in NPHS and > or = 1 grade in MRS. Intention-to-treat analysis of all patients at one year yielded improvement of 57% in NPHS and 59% in MRS. Efficacy analysis, excluding comorbidity unrelated to NPH, revealed positive predictive values of around 80% at Rcsf < 18, and between 90% and 100% at Rcsf > or = 18 mm Hg/ml/min. For Rcsf > or = 18, the likelihood ratios were also higher. We conclude that the best predictor of the response to shunting is an Rcsf > or = 18 mm Hg/ml/min. Since two-thirds of the patients with Rcsf < 18 showed improvement as well, these patients should not be denied shunting.

Pediatric hydrocephalus: 40-year outcomes in 128 hydrocephalic patients treated with shunts during childhood. Assessment of surgical outcome, work participation, and health-related quality of life.

PubMed

Paulsen, Anne Henriette; Lundar, Tryggve; Lindegaard, Karl-Fredrik

2015-12-01

Treatment for hydrocephalus has not advanced appreciably since the advent of CSF shunts more than 50 years ago. The outcome for pediatric patients with hydrocephalus has been the object for several studies; however, much uncertainty remains regarding the very long term outcome for these patients. Shunting became the standard treatment for hydrocephalus in Norway during the 1960s, and the first cohorts from this era have now reached middle age. Therefore, the objective of this study was to review surgical outcome, mortality, social outcome, and health-related quality of life in middle-aged patients treated for hydrocephalus during childhood. Data were collected in all patients, age 14 years or less, who required a CSF shunt during the years 1967-1970. Descriptive statistics were assessed regarding patient characteristics, surgical features, social functioning, and work participation. The time and cause of death, if applicable, were also determined. Kaplan-Meier survival estimates were used to determine the overall survival of patients. Information regarding self-perceived health and functional status was assessed using the 36-Item Short Form Health Survey (SF-36) and the Barthel Index score. A total of 128 patients were included in the study, with no patient lost to follow-up. Of the 128 patients in the study, 61 (47.6%) patients died during the 42-45 years of observation. The patients who died belonged to the tumor group (22 patients) and the myelomeningocele group (13 patients). The mortality rate was lowered to 39% if the patients with tumors were excluded. The overall mortality rates at 1, 2, 10, 20, and 40 years from time of initial shunt insertion were 16%, 24%, 31%, 40%, and 48% respectively. The incidence of shunt-related mortality was 8%. The majority of children graduated from a normal school (67%) or from a school specializing in education for physically handicapped children (20%). Self-perceived health was significantly poorer in 6 out of 8 domains assessed by SF-36 as compared with the background population. Functional status among the survivors varied greatly during the follow-up period, but the majority of patients were self-dependent. A total of 56% of the patients were socially independent, and 42% of the patients were employed. Approximately half of the patients are still alive. During the 42-45 year follow-up period, the mortality rate was 48%. Two deaths were due to acute shunt failure, and at least 8% of the deaths were shunt related (probable or late onset). The morbidity in middle-aged individuals treated for pediatric hydrocephalus is considerable. The late mortality rate was low, but not negligible. Twelve patients died during the last 2 decades, 1 of whom died because of acute shunt failure. Although the shunt revision rate was decreasing during the study period, many patients required shunt surgery during adulthood. Forty-one revisions in 21 patients were performed during the last decade. Thus, there is an obvious need for life-long follow-up in these patients.

Lumboperitoneal Shunts for the Treatment of Idiopathic Normal Pressure Hydrocephalus: A Comparison of Small-Lumen Abdominal Catheters to Gravitational Add-On Valves in a Single Center.

PubMed

Nakajima, Madoka; Miyajima, Masakazu; Akiba, Chihiro; Ogino, Ikuko; Kawamura, Kaito; Sugano, Hidenori; Hara, Takeshi; Tange, Yuichi; Fusegi, Keiko; Karagiozov, Kostadin; Arai, Hajime

2018-04-23

Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. To investigate whether LPSs, including gravitational "add-on" and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

Hydrostatic and hydrodynamic considerations in shunted normal pressure hydrocephalus.

PubMed

de Jong, D A; Delwel, E J; Avezaat, C J

2000-01-01

Symptoms of overdrainage, a frequent complication following shunting procedures especially in patients with normal-pressure hydrocephalus (NPH), are presumed to be caused by siphoning: gravity-enhanced flow of cerebro spinal fluid (CSF) through shunts in upright position. A critical reappraisal of siphoning and overdrainage (OD) is presented considering the occurrence of subdural hygromas (SDH) encountered in a group of patients shunted for NPH. The patients participated in the multicentre Dutch NPH study: 101 NPH patients were randomised for treatment with shunts with low or medium-high working pressure. Treatment with shunts with low working pressure resulted in an increased incidence of SDH (iSDH). Current physiological concepts of overdrainage are discussed and criticised. A new theory is presented on the basis of general physiological considerations. The theoretical model proposed yields a revised explanation for the origin of extremely low ventricular pressure in the upright position found with overdrainage. The efficacy of siphoning-preventing shunts and subtemporal decompression is explored in the light of the proposed theory.

Ammonia concentrations in arterial blood, venous blood, and cerebrospinal fluid of dogs with and without congenital extrahepatic portosystemic shunts.

PubMed

Or, Matan; Devriendt, Nausikaa; Kitshoff, Adriaan M; Peremans, Kathelijne; Vandermeulen, Eva; Paepe, Dominique; Polis, Ingeborgh; Martlé, Valentine; de Rooster, Hilde

2017-11-01

OBJECTIVE To compare ammonia concentrations in arterial blood, venous blood, and CSF samples of dogs with and without extrahepatic portosystemic shunts (EHPSS). ANIMALS 19 dogs with congenital EHPSS and 6 healthy control dogs. PROCEDURES All dogs underwent a physical examination and then were anesthetized for transsplenic portal scintigraphy to confirm the presence or absence of EHPSS. While dogs were anesthetized, arterial and venous blood samples and a CSF sample were simultaneously collected for determination of ammonia concentration, which was measured by use of a portable blood ammonia analyzer (device A) and a nonportable biochemical analyzer (device B). Results were compared between dogs with EHPSS and control dogs. RESULTS Arterial, venous, and CSF ammonia concentrations for dogs with EHPSS were significantly greater than those for control dogs. For dogs with EHPSS, ammonia concentrations in both arterial and venous blood samples were markedly increased from the reference range. There was a strong positive correlation between arterial and venous ammonia concentrations and between blood (arterial or venous) and CSF ammonia concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that blood and CSF ammonia concentrations in dogs with EHPSS were greater than those for healthy dogs and were strongly and positively correlated, albeit in a nonlinear manner. This suggested that the permeability of the blood-brain barrier to ammonia may be abnormally increased in dogs with EHPSS, but further investigation of the relationship between blood or CSF ammonia concentration and clinical signs of hepatic encephalopathy or the surgical outcome for dogs with EHPSS is warranted.

Congenital Hydrocephalus.

PubMed

Estey, Chelsie M

2016-03-01

There are several types of hydrocephalus, which are characterized based on the location of the cerebrospinal fluid (CSF) accumulation. Physical features of animals with congenital hydrocephalus may include a dome-shaped skull, persistent fontanelle, and bilateral ventrolateral strabismus. Medical therapy involves decreasing the production of CSF. The most common surgical treatment is placement of a ventriculoperitoneal shunt. Postoperative complications may include infection, blockage, drainage abnormalities, and mechanical failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroimaging in normal pressure hydrocephalus

PubMed Central

Damasceno, Benito Pereira

2015-01-01

Normal pressure hydrocephalus (NPH) is a syndrome characterized by the triad of gait disturbance, mental deterioration and urinary incontinence, associated with ventriculomegaly and normal cerebrospinal fluid (CSF) pressure. The clinical presentation (triad) may be atypical or incomplete, or mimicked by other diseases, hence the need for supplementary tests, particularly to predict postsurgical outcome, such as CSF tap-tests and computed tomography (CT) or magnetic resonance imaging (MRI). The CSF tap-test, especially the 3 to 5 days continuous external lumbar drainage of at least 150 ml/day, is the only procedure that simulates the effect of definitive shunt surgery, with high sensitivity (50-100%) and high positive predictive value (80-100%). According to international guidelines, the following are CT or MRI signs decisive for NPH diagnosis and selection of shunt-responsive patients: ventricular enlargement disproportionate to cerebral atrophy (Evans index >0.3), and associated ballooning of frontal horns; periventricular hyperintensities; corpus callosum thinning and elevation, with callosal angle between 40º and 90º; widening of temporal horns not fully explained by hippocampal atrophy; and aqueductal or fourth ventricular flow void; enlarged Sylvian fissures and basal cistern, and narrowing of sulci and subarachnoid spaces over the high convexity and midline surface of the brain. On the other hand, other imaging methods such as radionuclide cisternography, SPECT, PET, and also DTI or resting-state functional MRI, although suitable for NPH diagnosis, do not yet provide improved accuracy for identifying shunt-responsive cases. PMID:29213984

Predictors of hydrocephalus as a complication of non-traumatic subarachnoid hemorrhage: a retrospective observational cohort study in 107 patients.

PubMed

Vinas Rios, Juan Manuel; Sanchez-Aguilar, Martin; Kretschmer, Thomas; Heinen, Christian; Medina Govea, Fatima Azucena; Jose Juan, Sanchez-Rodriguez; Schmidt, Thomas

2018-01-01

The predictors of shunt dependency such as amount of subarachnoid blood, acute hydrocephalus (HC), mode of aneurysm repair, clinical grade at admission and cerebro spinal fluid (CSF) drainage in excess of 1500 ml during the 1st week after the subarachnoid hemorrhage (SAH) have been identified as predictors of shunt dependency. Therefore our main objective is to identify predictors of CSF shunt dependency following non-traumatic subarachnoid hemorrhage. We performed a retrospective study including patients from January 1st 2012 to September 30th 2014 between 16 and 89 years old and had a non-traumatic subarachnoid hemorrhage in cranial computed tomography (CCT). We excluded patients with the following characteristics: Patients who died 3 days after admittance, lesions in brainstem, previous surgical treatment in another clinic, traumatic brain injury, pregnancy and disability prior to SAH.We performed a descriptive and comparative analysis as well as a logistic regression with the variables that showed a significant difference ( p  < 0.05). Hence we identified the variables concerning HC after non traumatic SAH and its correlation. One hundred and seven clinical files of patients with non-traumatic SAH were analyzed. Twenty one (48%) later underwent shunt treatment. Shunt patients had significantly clinical and corroborated with doppler ultrasonography vasospasmus ( p  = 0.015), OR = 5.2. The amount of subarachnoidal blood according to modified Fisher grade was ( p  = 0.008) OR = 10.9. Endovascularly treated patients were less often shunted as compared with those undergoing surgical aneurysm repair ( p  = 0.004). Vasospasmus and a large amount of ventricular blood seem to be a predictor concerning hydrocephalus after non-traumatic SAH. Hence according to our results the presence of these two variables could alert the treating physician in the decision whether an early shunt implantation < 7 days after SAH should be necessary.

Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes

PubMed Central

Jurjević, Ivana; Miyajima, Masakazu; Ogino, Ikuko; Akiba, Chihiro; Nakajima, Madoka; Kondo, Akihide; Kikkawa, Mika; Kanai, Mitsuyasu; Hattori, Nobutaka; Arai, Hajime

2016-01-01

Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer’s disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = –0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion. Conclusion: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses. PMID:27911315

Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes.

PubMed

Jurjević, Ivana; Miyajima, Masakazu; Ogino, Ikuko; Akiba, Chihiro; Nakajima, Madoka; Kondo, Akihide; Kikkawa, Mika; Kanai, Mitsuyasu; Hattori, Nobutaka; Arai, Hajime

2017-01-01

Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer's disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = -0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion. Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.

Improvised external ventricular drain in neurosurgery: A Nigerian tertiary hospital experience

PubMed Central

Ojo, O. A.; Asha, M. A.; Bankole, O. B.; Kanu, O. O.

2015-01-01

Background: The most common type of hydrocephalus in developing countries is post infective hydrocephalus. Infected cerebrospinal fluid (CSF) however cannot be shunted for the reason that it will block the chamber of the ventriculo-peritoneal (VP) shunt due to its high protein content. In centers where standard external ventricular drain (EVD) sets are not available, improvised feeding tube can be used. Aim: The main focus of this study is to encourage the use of improvised feeding tube catheters for EVD when standard sets are not available to improve patients’ survival. Methodology: This was a prospective study. Consecutive patients with hydrocephalus that cannot be shunted immediately for high chances of shunt failure or signs of increasing intracranial pressure were recruited into the study. Other inclusion criteria were preoperative brain tumor with possibility of blocked CSF pathway and massive intraventricular hemorrhage necessitating ventricular drainage as a salvage procedure. Standard EVD set is not readily available and too expensive for most of the parents to afford. Improvised feeding tube is used to drain/divert CSF using the standard documented procedure for EVD insertion. Outcome is measured and recorded. Results: A total of 28 patients were recruited into the study over a time frame of 2 years. There were 19 (67.9%) male and 9 (32.1%) females with a ratio of about 2:1. Age ranges varied from as low as 7 days to 66 years. The median age of the study sample was 6.5 months while the mean was 173.8 months. Duration of EVD varied from 2 days to 11 days with a median of 7 while the average was 6 days. Eventual outcome following the procedure of EVD showed that 19 (67.9%) survived and were discharged either to go home or to have VP shunt afterwards while 8 (28.6%) of the patients died. Conclusions: External ventricular drain can and should be done when it is necessary. Potential mortalities could be reduced by the improvised drainage using a standard feeding tube as described. PMID:26167009

Stereotactic CO2 laser therapy for hydrocephalus

NASA Astrophysics Data System (ADS)

Kozodoy-Pins, Rebecca L.; Harrington, James A.; Zazanis, George A.; Nosko, Michael G.; Lehman, Richard M.

1994-05-01

A new fiber-optic delivery system for CO2 radiation has been used to successfully treat non-communicating hydrocephalus. This system consists of a hollow sapphire waveguide employed in the lumen of a stereotactically-guided neuroendoscope. CO2 gas flows through the bore of the hollow waveguide, creating a path for the laser beam through the cerebrospinal fluid (CSF). This delivery system has the advantages of both visualization and guided CO2 laser radiation without the same 4.3 mm diameter scope. Several patients with hydrocephalus were treated with this new system. The laser was used to create a passage in the floor of the ventricle to allow the flow of CSF from the ventricles to the sub-arachnoid space. Initial postoperative results demonstrated a relief of the clinical symptoms. Long-term results will indicate if this type of therapy will be superior to the use of implanted silicone shunts. Since CO2 laser radiation at 10.6 micrometers is strongly absorbed by the water in tissue and CSF, damage to tissue surrounding the lesion with each laser pulse is limited. The accuracy and safety of this technique may prove it to be an advantageous therapy for obstructive hydrocephalus.

Quantitative assessment of cerebrospinal fluid hydrodynamics using a phase-contrast cine MR image in hydrocephalus.

PubMed

Kim, D S; Choi, J U; Huh, R; Yun, P H; Kim, D I

1999-09-01

This investigation was undertaken to characterize CSF flow at the level of the aqueduct of Sylvius with a phase-contrast cine MR pulse sequence in 28 healthy volunteers. Sixteen patients with obstructive hydrocephalus and 11 patients with normal pressure hydrocephalus (NPH) were investigated with the same sequence before and after CSF diversion. The peak CSF flow velocity and stroke volume in the aqueduct increased significantly in the NPH group and decreased significantly in the obstructive hydrocephalus group. After lumboperitoneal shunting in the NPH group, the retrograde flow of CSF was anterogradely converted and the peak flow velocities decreased somewhat. The clinical diagnosis of NPH was well correlated with the results of cine MRI. After endoscopic III ventriculostomy in the obstructive hydrocephalus group we noted increased CSF flow velocity with markedly increased stroke volume at the prepontine cistern. Phase-contrast cine MR is useful in evaluating CSF dynamics in patients with hyperdynamic aqueductal CSF or aqueductal obstruction.

Paradoxical Brain Herniation After Decompressive Craniectomy Provoked by Drainage of Subdural Hygroma.

PubMed

Nasi, Davide; Dobran, Mauro; Iacoangeli, Maurizio; Di Somma, Lucia; Gladi, Maurizio; Scerrati, Massimo

2016-07-01

Paradoxical brain herniation (PBH) is a rare and potentially life-threatening complication of decompressive craniectomy (DC) and results from the combined effects of brain gravity, atmospheric pressure and intracranial hypotension causing herniation in the direction opposite to the site of the DC with subsequent brainstem compression. To date, the cases of PBH reported in literature are spontaneous or provoked by a lumbar puncture, a cerebrospinal fluid (CSF) shunt, or ventriculostomy. We present an uncommon case of PBH provoked by percutaneous drainage of a huge subdural hygroma (SH) ipsilateral to the decompressive craniectomy causing mass effect and neurologic deterioration. After percutaneous evacuation of SH, the patient became unresponsive with dilated and fixed left pupil. A brain computed tomography scan showed marked midline shift in the direction opposite to the craniectomy site with subfalcine herniation and effacement of the peripontine cisterns. Paradoxical brain herniation (PBH) was diagnosed. Conservative treatment failed, and the patient required an emergency cranioplasty for reverse PBH. The present case highlights the possibility that all forms of CSF depletion, including percutaneous drainage of subdural CSF collection and not only CSF shunting and/or lumbar puncture, can be dangerous for patients with large craniotomies and result in PBH. Moreover, an emergency cranioplasty could represent a safe and effective procedure in patients not responding to conservative treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

How frequently external ventricular drainage device should be changed in children with ventriculoperitonel shunt infection?

PubMed Central

Gulsen, Ismail; Ak, Hakan; Demir, Nihat; Sosuncu, Enver; Arslan, Mehmet

2015-01-01

Objective: The purpose of the presenting study was to determine how frequently external ventricular drainage (EVD) device should be changed in children with ventriculopertienal shunt (VPS) infection during prolonged intravenous antimicrobial therapy. Methods: In this retrospective study, 25 children with VPS infection were evaluated between January 2012 and December 2013. In these children VPS was surgically removed and appropriate antimicrobial therapy was administered according to cerebrospinal culture results. Data noted about how frequently EVD device had been changed, the number of cells on direct observation of cerebrospinal fluid (CSF), glucose and protein levels of CSF, and CSF culture results were obtained from patients’ records. Results: Total 25 children were included in the study. The median age was three months (1 and 65 months). In 44% of children, Staphylococcus epidermidis was isolated. During treatment period, EVD catheter has changed one to six times. A total of 68 EVD catheters were changed in these patients. When the duration of ventriculostomy catheter and leukocyte count in CSF were evaluated on daily basis, leukocyte count was decreased 5 units per day in children whose catheter remained less than 10 days. However, in children whose catheter remained more than 10 days leukocyte count was decreased 2.21 units per day. Conclusions: In children with VPS infection, EVD device should be changed at every 10 days for the rapid resolution of the infection. PMID:26101506

Normal pressure hydrocephalus in patients with myelomeningocele.

PubMed

Hammock, M K; Milhorat, T H; Baron, I S

1976-01-01

Although the syndrome of normal pressure hydrocephalus (NPH) was described in the adult as early as 1964, it has only recently been recognized in the child. In this preliminary report, eight myelomeningocele patients with presumed NPH were evaluated before and after ventricular shunting procedures. Cranial computed tomography and serial psychological testing have proved to be particularly valuable both in the pre-operative and post-operative assessment of these patients and have the distinct advantage of being simple, non-invasive diagnostic measures. Continuous intra-ventricular pressure monitoring has shown what promises to be characteristic elevated pressure plateaux imposed on normal baseline cerebrospinal fluid (CSF) pressures in so-called NPH but is a more difficult clinical procedure, necessarily associated with potential complications. Although decreasing response to growth-stimulating hormone can be demonstrated in patients with long-standing hydrocephalus, this endocrine malfunction cannot be considered an early indicator of intracranial pathology. Single IQ scores are inadequate measures of intellectural function in children with NPH and serial examinations should be carried out. Detailed neuropsychological testing will document performance IQ scores well below verbal IQ scores and will generally show failure of psychomotor development to keep pace with chronological ageing. Initial studies indicate that improved performance scores can be expected within 1 1/2 to 3 months following successful ventricular shunting operations, and that any downward trend in pre-operative test scoring can at least be reversed. Statistically significant improvements in full-scale IQ scores have not been seen, however, before the end of the first post-operative year. Clinically, improved attentiveness and sociability, and decreased spasticity (if present prior to surgery) can be expected following shunting. Over-all, ventriculomegaly, normal CSF pressure, stable head size, and non-progressive neurological symptoms cannot be regarded as sufficient criteria for the diagnosis of an arrested state of hydrocephalus, and should suggest NPH, especially in those children who demonstrate a discrepancy between performance and verbal IQ scores and who fail to exhibit continuing psychomotor development with advancing age.

Shunting outcomes in posthemorrhagic hydrocephalus: results of a Hydrocephalus Clinical Research Network prospective cohort study.

PubMed

Wellons, John C; Shannon, Chevis N; Holubkov, Richard; Riva-Cambrin, Jay; Kulkarni, Abhaya V; Limbrick, David D; Whitehead, William; Browd, Samuel; Rozzelle, Curtis; Simon, Tamara D; Tamber, Mandeep S; Oakes, W Jerry; Drake, James; Luerssen, Thomas G; Kestle, John

2017-07-01

OBJECTIVE Previous Hydrocephalus Clinical Research Network (HCRN) retrospective studies have shown a 15% difference in rates of conversion to permanent shunts with the use of ventriculosubgaleal shunts (VSGSs) versus ventricular reservoirs (VRs) as temporization procedures in the treatment of hydrocephalus due to high-grade intraventricular hemorrhage (IVH) of prematurity. Further research in the same study line revealed a strong influence of center-specific decision-making on shunt outcomes. The primary goal of this prospective study was to standardize decision-making across centers to determine true procedural superiority, if any, of VSGS versus VR as a temporization procedure in high-grade IVH of prematurity. METHODS The HCRN conducted a prospective cohort study across 6 centers with an approximate 1.5- to 3-year accrual period (depending on center) followed by 6 months of follow-up. Infants with premature birth, who weighed less than 1500 g, had Grade 3 or 4 IVH of prematurity, and had more than 72 hours of life expectancy were included in the study. Based on a priori consensus, decisions were standardized regarding the timing of initial surgical treatment, upfront shunt versus temporization procedure (VR or VSGS), and when to convert a VR or VSGS to a permanent shunt. Physical examination assessment and surgical technique were also standardized. The primary outcome was the proportion of infants who underwent conversion to a permanent shunt. The major secondary outcomes of interest included infection and other complication rates. RESULTS One hundred forty-five premature infants were enrolled and met criteria for analysis. Using the standardized decision rubrics, 28 infants never reached the threshold for treatment, 11 initially received permanent shunts, 4 were initially treated with endoscopic third ventriculostomy (ETV), and 102 underwent a temporization procedure (36 with VSGSs and 66 with VRs). The 2 temporization cohorts were similar in terms of sex, race, IVH grade, head (orbitofrontal) circumference, and ventricular size at temporization. There were statistically significant differences noted between groups in gestational age, birth weight, and bilaterality of clot burden that were controlled for in post hoc analysis. By Kaplan-Meier analysis, the 180-day rates of conversion to permanent shunts were 63.5% for VSGS and 74.0% for VR (p = 0.36, log-rank test). The infection rate for VSGS was 14% (5/36) and for VR was 17% (11/66; p = 0.71). The overall compliance rate with the standardized decision rubrics was noted to be 90% for all surgeons. CONCLUSIONS A standardized protocol was instituted across all centers of the HCRN. Compliance was high. Choice of temporization techniques in premature infants with IVH does not appear to influence rates of conversion to permanent ventricular CSF diversion. Once management decisions and surgical techniques are standardized across HCRN sites, thus minimizing center effect, the observed difference in conversion rates between VSGSs and VRs is mitigated.

Pathogen Identification by Multiplex LightMix Real-Time PCR Assay in Patients with Meningitis and Culture-Negative Cerebrospinal Fluid Specimens

PubMed Central

Wagner, Karoline; Springer, Burkard; Pires, Valeria P.

2017-01-01

ABSTRACT Acute bacterial meningitis is a medical emergency, and delays in initiating effective antimicrobial therapy result in increased morbidity and mortality. Culture-based methods, thus far considered the “gold standard” for identifying bacterial microorganisms, require 24 to 48 h to provide a diagnosis. In addition, antimicrobial therapy is often started prior to clinical sample collection, thereby decreasing the probability of confirming the bacterial pathogen by culture-based methods. To enable a fast and accurate detection of the most important bacterial pathogens causing meningitis, namely, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes, we evaluated a commercially available multiplex LightMix real-time PCR (RT-PCR) in 220 cerebrospinal fluid (CSF) specimens. The majority of CSF samples were collected by lumbar puncture, but we also included some CSF samples from patients with symptoms of meningitis from the neurology department that were recovered from shunts. CSF samples were analyzed by multiplex RT-PCR enabling a first diagnosis within a few hours after sample arrival at our institute. In contrast, bacterial identification took between 24 and 48 h by culture. Overall, a high agreement of bacterial identification between culture and multiplex RT-PCR was observed (99%). Moreover, multiplex RT-PCR enabled the detection of pathogens, S. pneumoniae (n = 2), S. agalactiae (n = 1), and N. meningitidis (n = 1), in four culture-negative samples. As a complement to classical bacteriological CSF culture, the LightMix RT-PCR assay proved to be valuable by improving the rapidity and accuracy of the diagnosis of bacterial meningitis. PMID:29237781

Delayed intracerebral and subdural hematomas after ventriculo-peritoneal shunt in a child: A case report and review of the literature.

PubMed

Coulibaly, O; Dama, M; Diallo, O; Li, G; Sogoba, Y; Kanikomo, D

2016-04-01

Ventriculo-peritoneal shunt (VPS) continues to remain the main diverted method to drain the cerebrospinal fluid (CSF) from the ventricles to the peritoneal cavity. It has some complications that must be managed promptly to avoid any eventual fatal evolution. The association of delayed intracerebral and subdural hematomas after VPS insertion is a very rare complication and has, to our knowledge, never previously been reported in the literature. We report a very uncommon association of this entity occurring 11months after a shunt placement in a 13-year-old boy and discuss the likely pathogenesis, as well as the clinical and the radiological data. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Surgical site infections following craniotomy focusing on possible post-operative acquisition of infection: prospective cohort study.

PubMed

Sneh-Arbib, O; Shiferstein, A; Dagan, N; Fein, S; Telem, L; Muchtar, E; Eliakim-Raz, N; Rubinovitch, B; Rubin, G; Rappaport, Z H; Paul, M

2013-12-01

Neurosurgery is characterized by a prolonged risk period for surgical site infection (SSI), mainly related to the presence of cerebrospinal fluid (CSF) drains. We aimed to examine factors associated with post-neurosurgical SSIs, focusing on post-operative factors. A prospective cohort study was conducted in a single center over a period of 18 months in Israel. Included were adult patients undergoing clean or clean-contaminated craniotomy, including craniotomies with external CSF drainage or shunts. SSIs were defined by the Centers for Disease Control and Prevention (CDC) criteria for healthcare-associated infections. All patients were followed up for 90 days and those with foreign body insertion for 1 year. We compared patients with and without SSI. A multivariable regression analysis for SSI was conducted including uncorrelated variables significantly associated with SSI. A total of 502 patients were included, with 138 (27.5%) undergoing emergent or urgent craniotomy. The overall SSI rate was 5.6% (28 patients), of which 3.2% (16 patients) were intracerebral. Non-elective surgery, external CSF drainage/monitoring devices, re-operation, and post-operative respiratory failure were independently associated with subsequent SSI. External CSF devices was the only significant risk factor for intracerebral SSIs (p < 0.001). Internal shunts or other foreign body insertions were not associated with SSIs. A phenotypically identical isolate to that causing the SSI was isolated from respiratory secretions prior to the SSI in 4/9 patients with microbiologically documented intracerebral SSIs. Patients with SSIs had longer hospital stay, poorer functional capacity on discharge, and higher 90-day mortality. We raise the possibility of post-operative infection acquisition through external CSF devices. Standard operating procedures for their maintenance are necessary.

Two-dimensional finite element modelling of the neonatal head.

PubMed

Gibson, A; Bayford, R H; Holder, D S

2000-02-01

Electrical impedance tomography (EIT) could allow the early diagnosis of infant brain injury following birth asphyxia. The purpose of this work was to determine the effect of variations in skull, scalp or cerebrospinal fluid (CSF) resistivity, as these vary in clinical conditions and could degrade image quality. These factors were investigated using finite element models of the adult and neonatal head. The results suggest that there is a wide range over which the resistivity of the neonatal skull has little effect on the sensitivity to a central impedance change. The scalp and CSF appear to shunt current away from the brain; when their resistivity was decreased from normal values, this shunting effect increased and caused a decrease in sensitivity to a central resistance change. The resistivity of neonatal skull has not, to our knowledge, been directly measured and will anyway vary within and between individuals; this work suggests that EIT will be relatively insensitive to variations in neonatal skull impedance.

Decompressive craniectomy and hydrocephalus: proposal of a therapeutic flow chart.

PubMed

Peraio, Simone; Calcagni, Maria Lucia; Mattoli, Maria Vittoria; Marziali, Giammaria; DE Bonis, Pasquale; Pompucci, Angelo; Anile, Carmelo; Mangiola, Annunziato

2017-12-01

Decompressive craniectomy (DC) may be necessary to save the lives of patients suffering from intracranial hypertension. However, this procedure is not complication-free. Its two main complications are hydrocephalus and the sinking skin-flap syndrome (SSFS). The radiological findings and the clinical evaluation may be not enough to decide when and/or how to treat hydrocephalus in a decompressed patient. SSFS and hydrocephalus may be not unrelated. In fact, a patient affected by hydrocephalus, after the ventriculo-peritoneal shunt, can develop SSFS; on the other hand, SSFS per se can cause hydrocephalus. Treating hydrocephalus in decompressed patients can be challenging. Radiological findings and clinical evaluation may not be enough to define the most appropriate therapeutic strategy. Cerebrospinal fluid (CSF) dynamics and metabolic evaluations can represent important diagnostic tools for assessing the need of a CSF shunt in patients with a poor baseline neurologic status. Based on our experience, we propose a flow chart for treating decompressed patients affected by ventriculomegaly.

Numerical simulation of cerebrospinal fluid hydrodynamics in the healing process of hydrocephalus patients

NASA Astrophysics Data System (ADS)

Gholampour, S.; Fatouraee, N.; Seddighi, A. S.; Seddighi, A.

2017-05-01

Three-dimensional computational models of the cerebrospinal fluid (CSF) flow and brain tissue are presented for evaluation of their hydrodynamic conditions before and after shunting for seven patients with non-communicating hydrocephalus. One healthy subject is also modeled to compare deviated patients data to normal conditions. The fluid-solid interaction simulation shows the CSF mean pressure and pressure amplitude (the superior index for evaluation of non-communicating hydrocephalus) in patients at a greater point than those in the healthy subject by 5.3 and 2 times, respectively.

Long-term follow-up of successful treatment for dandy-walker syndrome (DWS).

PubMed

Lin, Jun; Liang, Guobiao; Liang, Yong; Kou, Yun

2015-01-01

Various managements of Dandy-Walker syndrome (DWS) from open excision of the cysts to CSF diversion have been reported. However, optimal treatment for DWS remains elusive. Cyst fenestration was employed firstly, but failed 15 days after the surgery. Then a ventriculoperitoneal (VP) shunt was inserted and the patient discharged from hospital 13 days after the second surgery. During the 12-year follow-up, CT scanning, MRI, and X-radiation were performed. CT scanning showed that the size of ventricular system gradually returned to normal. MRI revealed similar changes of the ventricular system, and further revealed the development of supratentorial brain. The results of X-radiation during the follow-up years showed that the peritoneal end of the shunt might be already out of the abdominal cavity. Slow refilling of the shunt valve may suggest that the shunt could be probably not functional. The treatment of the patient was successfully, and the abnormal cerebral ventricle system gradually recovered during the 12-year follow-up. Because the patient might be probably independent on the shunt, further choice of the shunt removal should be thinking thoroughly, considering both safety and quality of life for the patient.

Long-term follow-up of successful treatment for dandy-walker syndrome (DWS)

PubMed Central

Lin, Jun; Liang, Guobiao; Liang, Yong; Kou, Yun

2015-01-01

Background: Various managements of Dandy-Walker syndrome (DWS) from open excision of the cysts to CSF diversion have been reported. However, optimal treatment for DWS remains elusive. Methods: Cyst fenestration was employed firstly, but failed 15 days after the surgery. Then a ventriculoperitoneal (VP) shunt was inserted and the patient discharged from hospital 13 days after the second surgery. During the 12-year follow-up, CT scanning, MRI, and X-radiation were performed. Results: CT scanning showed that the size of ventricular system gradually returned to normal. MRI revealed similar changes of the ventricular system, and further revealed the development of supratentorial brain. The results of X-radiation during the follow-up years showed that the peritoneal end of the shunt might be already out of the abdominal cavity. Slow refilling of the shunt valve may suggest that the shunt could be probably not functional. Conclusion: The treatment of the patient was successfully, and the abnormal cerebral ventricle system gradually recovered during the 12-year follow-up. Because the patient might be probably independent on the shunt, further choice of the shunt removal should be thinking thoroughly, considering both safety and quality of life for the patient. PMID:26770421

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus.

PubMed

Schirinzi, Tommaso; Sancesario, Giulia Maria; Di Lazzaro, Giulia; D'Elia, Alessio; Imbriani, Paola; Scalise, Simona; Pisani, Antonio

2018-04-01

Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers. However, neuropathology of iNPH is so rich and heterogeneous that many processes can be tracked in CSF, including Alzheimer's disease core pathology, subcortical degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has not been provided yet. In this brief survey, we thus attempted to summarize the main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic model. Although defined cut-off values for biomarkers are not available, a better knowledge of CSF characteristics may definitely assist in diagnosing the disease.

Treatment of posthemorrhagic hydrocephalus in premature infants with subcutaneous reservoir drainage.

PubMed

Yu, Bo; Li, Shasha; Lin, Zhenlang; Zhang, Nu

2009-01-01

To investigate the effectiveness of subcutaneous reservoir drainage as a treatment for the different types of posthemorrhagic hydrocephalus in premature infants. 11 premature infants with posthemorrhagic hydrocephalus underwent subcutaneous reservoir embedment surgery, and cerebrospinal fluid (CSF) was drained via the reservoir intermittently for 8 weeks. During the period of drainage, ultrasound and computerized tomography were used to measure ventricle size. CSF examinations were performed routinely to assess the presence of intraventricular hemorrhage (IVH) and/or infection. (1) Five infants were diagnosed as having obstructive hydrocephalus; 2 had nearly normal ventricle sizes with treatment and drainage was stopped after 8 weeks, 2 had nearly normal ventricle sizes after 4 more weeks of drainage, and 1 underwent ventriculoperitoneal shunt (V-P shunt) surgery due to failure of ventricle size reduction. (2) Six infants were diagnosed as having communicating hydrocephalus; 4 had further enlarged ventricle size after 8 weeks and underwent V-P shunt surgery, 1 had treatment aborted at week 8 of drainage, and only 1 had moderate reduction of ventricle size after 8 weeks. (3) None of the 11 infants had progressive IVH and/or intracranial infection during drainage. Subcutaneous reservoir drainage is a suitable and safe treatment for posthemorrhagic hydrocephalus in premature infants. It is more effective for obstructive hydrocephalus than for communicating hydrocephalus. Copyright (c) 2009 S. Karger AG, Basel.

Post-hemorrhagic hydrocephalus: Recent advances and new therapeutic insights.

PubMed

Chen, Qianwei; Feng, Zhou; Tan, Qiang; Guo, Jing; Tang, Jun; Tan, Liang; Feng, Hua; Chen, Zhi

2017-04-15

Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment. Non-surgical measures to reduce increased intracranial pressure (ICP) in PHH have shown little success and most patients will ultimately require surgical management, such as external ventricular drainage and shunting which mostly by inserting a CSF drainage shunt. Unfortunately, shunt complications are common and the optimum time for intervention is unclear. To date, there remains no comprehensive strategy for PHH management and it becomes imperative that to explore new therapeutic targets and methods for PHH. Over past decades, increasing evidence have indicated that hemorrhage-derived blood and subsequent metabolic products may play a key role in the development of IVH-, SAH- and TBI-associated PHH. Several intervention strategies have recently been evaluated and cross-referenced. In this review, we summarized and discussed the common aspects of hydrocephalus following IVH, SAH and TBI, relevant experimental animal models, clinical translation of in vivo experiments, and potential preventive and therapeutic targets for PHH. Copyright © 2017 Elsevier B.V. All rights reserved.

Vascular endothelial growth factor in the CSF of elderly patients with ventriculomegaly: variability, periodicity and levels in drainage responders and non-responders.

PubMed

Yang, Jun; Dombrowski, Stephen M; Krishnan, Chandra; Krajcir, Natalie; Deshpande, Abhishek; El-Khoury, Serge; Guruprakash, Deepti Kamasamudram; Luciano, Mark G

2013-09-01

The aim of this study was to examine lumbar CSF-VEGF levels from elderly patients with ventriculomegaly to evaluate the possible circadian or periodic concentration profile and relevance to the prediction of drainage response. Lumbar CSF samples were collected in 1-h interval over 35 h from 22 patients with ventriculomegaly. CSF-VEGF levels were measured to elucidate the possible circadian or periodic concentration profiles. These VEGF levels were evaluated for correlations with clinical response to CSF drainage, ventricle size and other clinical information. The 35-h CSF-VEGF levels demonstrated a periodic concentration pattern with significant episodic fluctuation with 3-5h intervals. CSF-VEGF levels in non-responder group in which patients did not show clinical improvement with CSF drainage were significantly higher than these in responder group. VEGF variation in hydrocephalus patients suggests its possible pathophysiological role in hydrocephalus. The periodic concentration pattern of CSF-VEGF must be considered when choosing the most appropriate time for sample collection or clinical manipulation. Increased VEGF level in patients who showed no improvement with CSF drainage suggests that a possible greater ischemic or vascular injury may play a role in these patients. Pending further studies, these results suggest that high VEGF levels have a potential application in predicting non-responder patients with CSF drainage and so reducing the morbidity and cost of drainage and shunting in these patients. Copyright © 2013. Published by Elsevier B.V.

Maladjustment of programmable ventricular shunt valves by inadvertent exposure to a common hospital device.

PubMed

Fujimura, R; Lober, R; Kamian, K; Kleiner, L

2018-01-01

Programmable ventricular shunt valves are commonly used to treat hydrocephalus. They can be adjusted to allow for varying amounts of cerebrospinal fluid (CSF) flow using an external magnetic programming device, and are susceptible to maladjustment from inadvertent exposure to magnetic fields. We describe the case of a 3-month-old girl treated for hydrocephalus with a programmable Strata TM II valve found at the incorrect setting on multiple occasions during her hospitalization despite frequent reprogramming and surveillance. We found that the Vocera badge, a common hands-free wireless communication system worn by our nursing staff, had a strong enough magnetic field to unintentionally change the shunt setting. The device is worn on the chest bringing it into close proximity to the shunt valve when care providers hold the baby, resulting in the maladjustment. Some commonly used medical devices have a magnetic field strong enough to alter programmable shunt valve settings. Here, we report that the magnetic field from the Vocera hands-free wireless communication system, combined with the worn position, results in shunt maladjustment for the Strata TM II valve. Healthcare facilities using the Vocera badges need to put protocols in place and properly educate staff members to ensure the safety of patients with Strata TM II valves.

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

PubMed

Karimy, Jason K; Duran, Daniel; Hu, Jamie K; Gavankar, Charuta; Gaillard, Jonathan R; Bayri, Yasar; Rice, Hunter; DiLuna, Michael L; Gerzanich, Volodymyr; Marc Simard, J; Kahle, Kristopher T

2016-11-01

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

["Normal pressure" hydrocephalus].

PubMed

Philippon, Jacques

2005-03-01

Normal pressure hydrocephalus (NPH) or, more precisely, chronic adult hydrocephalus, is a complex condition. Even if the basic mechanism is found in an impediment to CSF absorption, the underlying pathology is heterogeneous. In secondary NPH, the disruption of normal CSF pathways, following meningitis or sub-arachnoid haemorrhage, is responsible for ventricular dilatation. However, in about half of the cases, the etiology remains obscure. NPH is more frequently found in elderly people, probably in relation with the increased incidence of cerebrovascular disease. The diagnosis of NPH is based upon a triad of clinical symptoms. The main symptom is gait disturbances, followed by urinary incontinence and various degree of cognitive changes. The latter two symptoms are not prerequisites for the diagnosis. Radiological ventricular dilatation without cortical sulcal enlargement is a key factor, as well as substantial clinical improvement after CSF withdrawal (CSF tap test). Other CSF dynamic studies and various imaging investigations have been proposed to improve diagnostic accuracy, but no simple test can predict the results of CSF drainage. The current treatment is ventriculo-peritonial shunting, ideally using an adjustable valve. Results are directly dependent upon the accuracy of the preoperative diagnosis. Post-surgical complications may be observed in about 10% of cases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merchant, Thomas E., E-mail: thomas.merchant@stjude.or; Chitti, Ramana M.; Li Chenghong

Purpose: To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT). Methods: The study included 68 patients (median age +- standard deviation of 2.6 +- 3.8 years) who were followed for 5 years after receiving CRT (54-59.4 Gy) and were assessed for function of cranial nerves V to VII and IX to XII, motor weakness, and dysmetria. The mean (+- standard deviation) brainstem dose was 5,487 (+-464) cGy. Patients were divided into four groups representing those with normal baseline and follow-up, those with abnormal baseline and full recovery,more » those with abnormal baseline and partial or no recovery, and those with progressive deficits at 12 (n = 62 patients), 24 (n = 57 patients), and 60 (n = 50 patients) months. Grouping was correlated with clinical and treatment factors. Results: Risk factors (overall risk [OR], p value) associated with incomplete recovery included gender (male vs. female, OR = 3.97, p = 0.036) and gross tumor volume (GTV) (OR/ml = 1.23, p = 0.005) at 12 months, the number of resections (>1 vs. 1; OR = 23.7, p = 0.003) and patient age (OR/year = 0.77, p = 0.029) at 24 months, and cerebrospinal fluid (CSF) shunting (Yes vs. No; OR = 21.9, p = 0.001) and GTV volume (OR/ml = 1.18, p = 0.008) at 60 months. An increase in GTV correlated with an increase in the number of resections (p = 0.001) and CSF shunting (p = 0.035); the number of resections correlated with CSF shunting (p < 0.0001), and male patients were more likely to undergo multiple tumor resections (p = 0.003). Age correlated with brainstem volume (p < 0.0001). There were no differences in outcome based on the absolute or relative volume of the brainstem that received more than 54 Gy. Conclusions: Incomplete recovery of brainstem function after CRT for infratentorial ependymoma is related to surgical morbidity and the volume and the extent of tumor.« less

Surgical options for treatment of traumatic subdural hematomas in children younger than 2 years of age.

PubMed

Melo, José Roberto Tude; Di Rocco, Federico; Bourgeois, Marie; Puget, Stephanie; Blauwblomme, Thomas; Sainte-Rose, Christian; Meyer, Philippe G; Zerah, Michel

2014-04-01

Subdural hematoma (SDH) is the most common finding on cranial CT in pediatric victims of abusive head trauma (AHT). The hematomas are commonly bilateral and sometimes associated with interhemispheric hyperdensity and/or convexity hemorrhages. There is no consensus regarding the best surgical treatment in such cases nor are there standardized surgical protocols. The authors report their experience and discuss the routine surgical options in the management of traumatic SDH at a Level 1 Pediatric Trauma Center. In this paper, the authors describe a cross-sectional study with consecutive revision of data described in the medical records of Hôpital Universitaire Necker-Enfants Malades between January 2008 and January 2013. During this period, all children younger than 2 years of age who were admitted with a traumatic SDH identified on CT scans were included in this study. One hundred eighty-four children who had SDH and were younger than 2 years of age were included. Their median age was 5.8 months (range 5 days-23 months), and 70% of the children were male. On admission CT scans, the SDH was bilateral in 52% of cases and homogeneously hypodense in 77%. Neurosurgical treatment was undertaken in 111 children (60%) with an admission Glasgow Coma Scale score of 12 or less, bulging fontanels, or other signs suggestive of intracranial hypertension. The first surgical option was craniotomy in 1.8% (2) of these 111 cases, decompressive craniectomy in 1.8% (2), transcutaneous subdural puncture in 15% (17), external subdural drainage in 16% (18), subdural-subgaleal shunt placement in 17% (19), and subdural-peritoneal shunt placement in 48% (53). In 82% of the children initially treated with transcutaneous subdural puncture and in 50% of those treated with external subdural drainage, increase or persistence of the SDH, CSF or skin infection, or shunt system malfunction was observed and further surgical intervention was required. There was a 26% rate of complications in patients initially treated with a subdural-peritoneal shunt. Although 52% of the patients had bilateral SDH, bilateral drainage was only required in 9.4%. The choice of treatment should be determined by the clinical and radiological characteristics of the individual case. Although effective on an emergency basis, subdural puncture and external subdural drainage are frequently insufficient to obtain complete resolution of SDH, and temporary placement of a subdural-peritoneal shunt is needed in most cases.

CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

PubMed

Bradley, W G

2015-05-01

CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. © 2015 by American Journal of Neuroradiology.

Imaging normal pressure hydrocephalus: theories, techniques, and challenges.

PubMed

Keong, Nicole C H; Pena, Alonso; Price, Stephen J; Czosnyka, Marek; Czosnyka, Zofia; Pickard, John D

2016-09-01

The pathophysiology of NPH continues to provoke debate. Although guidelines and best-practice recommendations are well established, there remains a lack of consensus about the role of individual imaging modalities in characterizing specific features of the condition and predicting the success of CSF shunting. Variability of clinical presentation and imperfect responsiveness to shunting are obstacles to the application of novel imaging techniques. Few studies have sought to interpret imaging findings in the context of theories of NPH pathogenesis. In this paper, the authors discuss the major streams of thought for the evolution of NPH and the relevance of key imaging studies contributing to the understanding of the pathophysiology of this complex condition.

Frontal and occipital horn ratio is associated with multifocal intraparenchymal hemorrhages in neonatal shunted hydrocephalus.

PubMed

Oushy, Soliman; Parker, Jonathon J; Campbell, Kristen; Palmer, Claire; Wilkinson, Corbett; Stence, Nicholas V; Handler, Michael H; Mirsky, David M

2017-11-01

OBJECTIVE Placement of a cerebrospinal fluid diversion device (i.e., shunt) is a routine pediatric neurosurgical procedure, often performed in the first weeks of life for treatment of congenital hydrocephalus. In the postoperative period, shunt placement may be complicated by subdural, catheter tract, parenchymal, and intraventricular hemorrhages. The authors observed a subset of infants and neonates who developed multifocal intraparenchymal hemorrhages (MIPH) following shunt placement and sought to determine any predisposing perioperative variables. METHODS A retrospective review of the electronic medical record at a tertiary-care children's hospital was performed for the period 1998-2015. Inclusion criteria consisted of shunt placement, age < 30 days, and available pre- and postoperative brain imaging. The following data were collected and analyzed for each case: ventricular size ratios, laboratory values, clinical presentation, shunt and valve type, and operative timing and approach. RESULTS A total of 121 neonates met the inclusion criteria for the study, and 11 patients (9.1%) had MIPH following shunt placement. The preoperative frontal and occipital horn ratio (FOR) was significantly higher in the patients with MIPH than in those without (0.65 vs 0.57, p < 0.001). The change in FOR (∆FOR) after shunt placement was significantly greater in the MIPH group (0.14 vs 0.08, p = 0.04). Among neonates who developed MIPH, aqueductal stenosis was the most common etiology (45%). The type of shunt valve was associated with incidence of MIPH (p < 0.001). Preoperative clinical parameters, including head circumference, bulging fontanelle, and coagulopathy, were not significantly associated with development of MIPH. CONCLUSIONS MIPH represents an underrecognized complication of neonatal shunted hydrocephalus. Markers of severity of ventriculomegaly (FOR) and ventricular response to CSF diversion (∆FOR) were significantly associated with occurrence of MIPH. Choice of shunt and etiology of hydrocephalus were also significantly associated with MIPH. After adjusting for corrected age, etiology of hydrocephalus, and shunt setting, the authors found that ∆FOR after shunting was still associated with MIPH. A prospective study of MIPH prevention strategies and assessment of possible implications for patient outcomes is needed.

Magnetic resonance spectroscopic determination of a neuronal and axonal marker in white matter predicts reversibility of deficits in secondary normal pressure hydrocephalus

PubMed Central

Shiino, A; Nishida, Y; Yasuda, H; Suzuki, M; Matsuda, M; Inubushi, T

2004-01-01

Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. Objective: To investigate whether 1H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting. Methods: Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. Results: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. Conclusions: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage. PMID:15258216

Resistance to drainage of cerebrospinal fluid: clinical measurement and significance1

PubMed Central

Martins, Albert N.

1973-01-01

By infusing saline intrathecally at a constant rate until a new steady-state cerebrospinal fluid (CSF) pressure is attained, one can estimate clinically the apparent resistance (Ra) to drainage of CSF in mm saline/ml./minute. This intrathecal saline infusion test (ITSIT) was performed 36 times on 29 patients with diverse intracranial problems, and the results were analysed and, in most cases, compared with the pneumoencephalogram and the isotope cisternogram. The ITSIT is a safe, simple test to estimate Ra, but factors which are difficult to control (occult leaks from the subarachnoid space; independent fluctuations of CSF pressure) limit its reliability and clinical usefulness. If closely correlated with the clinical syndrome, the pneumoencephalogram, and the isotope cisternogram, an ITSIT may identify decisively the patient who needs a shunt. In addition the ITSIT offers another method by which to investigate the pathophysiological mechanisms of the various states of intracranial hypertension. Results from the test performed on four patients with intracranial hypertension of unknown cause (pseudotumor cerebri) suggest that the underlying mechanism in this condition is probably an impediment to normal CSF drainage. PMID:4541080

Pseudotumor cerebri following traumatic brain injury in a 29-year-old man

PubMed Central

Rahman, Mohammed Izad; Raveendran, Savitha; Kaliaperumal, Chandrasekaran; Marks, Charles

2012-01-01

We describe a case of pseudotumor cerebri in a young man developing 4 years post-traumatic brain injury (TBI). A 29-year-old man was admitted after sustaining a fall with headache, and no clinical deficits were noted on examination. CT brain demonstrated an extradural hematoma. This was successfully evacuated after his symptomatic worsening. Following this, he developed bone flap infection and had the infected bone flap removed. He developed chronic mild-to-moderate headache following these procedures, which failed to respond to medical treatment. Pseudotumor cerebri was diagnosed. A lumboperitoneal (LP) shunt, ventriculo-peritoneal (VP) shunt, and bitemporal craniectomy were performed as a part of management at different stages. Post-TBI patients may present with chronic headache and in such circumstances, a possibility of pseudotumor cerebri must be considered. Investigations should include neuroimaging in the form of MRI/MRV and fundoscopy to look for papilledema. Management in the form of CSF flow diversion techniques (VP and LP shunt) with medical management results in good clinical outcomes PMID:22690064

Endoscopic third ventriculostomy for treatment of adult hydrocephalus: long-term follow-up of 163 patients.

PubMed

Isaacs, Albert M; Bezchlibnyk, Yarema B; Yong, Heather; Koshy, Dilip; Urbaneja, Geberth; Hader, Walter J; Hamilton, Mark G

2016-09-01

OBJECTIVE The efficacy of endoscopic third ventriculostomy (ETV) for the treatment of pediatric hydrocephalus has been extensively reported in the literature. However, ETV-related long-term outcome data are lacking for the adult hydrocephalus population. The objective of the present study was to assess the role of ETV as a primary or secondary treatment for hydrocephalus in adults. METHODS The authors performed a retrospective chart review of all adult patients (age ≥ 18 years) with symptomatic hydrocephalus treated with ETV in Calgary, Canada, over a span of 20 years (1994-2014). Patients were dichotomized into a primary or secondary ETV cohort based on whether ETV was the initial treatment modality for the hydrocephalus or if other CSF diversion procedures had been previously attempted respectively. Primary outcomes were subjective patient-reported clinical improvement within 12 weeks of surgery and the need for any CSF diversion procedures after the initial ETV during the span of the study. Categorical and actuarial data analysis was done to compare the outcomes of the primary versus secondary ETV cohorts. RESULTS A total of 163 adult patients with symptomatic hydrocephalus treated with ETV were identified and followed over an average of 98.6 months (range 0.1-230.4 months). All patients presented with signs of intracranial hypertension or other neurological symptoms. The primary ETV group consisted of 112 patients, and the secondary ETV consisted of 51 patients who presented with failed ventriculoperitoneal (VP) shunts. After the initial ETV procedure, clinical improvement was reported more frequently by patients in the primary cohort (87%) relative to those in the secondary ETV cohort (65%, p = 0.001). Additionally, patients in the primary ETV group required fewer reoperations (p < 0.001), with cumulative ETV survival time favoring this primary ETV cohort over the course of the follow-up period (p < 0.001). Fifteen patients required repeat ETV, with all but one experiencing successful relief of symptoms. Patients in the secondary ETV cohort also had a higher incidence of complications, with one occurring in 8 patients (16%) compared with 2 in the primary ETV group (2%; p = 0.010), although most complications were minor. CONCLUSIONS ETV is an effective long-term treatment for selected adult patients with hydrocephalus. The overall ETV success rate when it was the primary treatment modality for adult hydrocephalus was approximately 87%, and 99% of patients experience symptomatic improvement after 2 ETVs. Patients in whom VP shunt surgery fails prior to an ETV have a 22% relative risk of ETV failure and an almost eightfold complication rate, although mostly minor, when compared with patients who undergo a primary ETV. Most ETV failures occur within the first 7 months of surgery in patients treated with primary ETV, but the time to failure is more prolonged in patients who present with failed previous shunts.

Big heads in Port Moresby General Hospital: an audit of hydrocephalus cases seen from 2003 to 2004.

PubMed

Kaptigau, W Matui; Ke, Liu; Rosenfeld, J V

2007-01-01

Hydrocephalus is a common neurosurgical problem in Port Moresby General Hospital (PMGH) contributing to 27 (24%) of the 114 neurosurgical operations done in 2003 and 2004. During the same period it was responsible for 25% of the cases seen in the neurosurgery clinic. To prospectively audit and follow up hydrocephalus cases in PMGH over 2 years from January 2003 to December 2004 and ascertain the causes and the outcome of treatment. All cases of hydrocephalus seen in 2003 and 2004 were categorized according to cause. The associated findings on ultrasound scan or CT (computed tomography) scan when available were noted. The subsequent progress was documented with and without treatment for at least 6 months. 61 cases of hydrocephalus were seen for surgical opinion. The age ranged from 4 weeks to 56 years. The commonest age group affected was in the first year of life (61% of cases). There were 34 cases (56%) of congenital hydrocephalus followed by 19 (31%) post meningitis and 8 (13%) due to tumour. There was only one case of myelomeningocele with concomitant hydrocephalus. Ventriculoperitoneal (VP) shunts were inserted in 24 cases. 3 shunts were bypasses from the posterior horn to the cisterna magna, making a total of 27 shunt operations. 9 shunts were performed for post-meningitic hydrocephalus, 15 for congenital stenosis and 3 for a posterior fossa tumour. 24 out of the 27 shunt operations were in children aged <9 months. Post-VP-shunt infection of 2 cases reported within 6 weeks of operation gave an infection rate of 7%. There was cerebrospinal fluid (CSF) leak in 2 cases with Pundez-type shunts. There were 2 shunt blocks needing revision. Shunt operations can be done in PMGH with good outcomes. The decision-making about surgery can be made on the basis of the enlarging head and the ultrasound findings.

The durability of endoscopic third ventriculostomy and ventriculoperitoneal shunts in children with hydrocephalus following posterior fossa tumor resection: a systematic review and time-to-failure analysis.

PubMed

Dewan, Michael C; Lim, Jaims; Shannon, Chevis N; Wellons, John C

2017-05-01

OBJECTIVE Up to one-third of patients with a posterior fossa brain tumor (PFBT) will experience persistent hydrocephalus mandating permanent CSF diversion. The optimal hydrocephalus treatment modality is unknown; the authors sought to compare the durability between endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) therapy in the pediatric population. METHODS The authors conducted a systematic review of articles indexed in PubMed between 1986 and 2016 describing ETV and/or VPS treatment success/failure and time-to-failure rate in patients < 19 years of age with hydrocephalus related to a PFBT. Additionally, the authors conducted a retrospective review of their institutional series of PFBT patients requiring CSF diversion. Patient data from the systematic review and from the institutional series were aggregated and a time-to-failure analysis was performed comparing ETV and VPS using the Kaplan-Meier method. RESULTS A total of 408 patients were included from 12 studies and the authors' institutional series: 284 who underwent ETV and 124 who underwent VPS placement. The analysis included uncontrolled studies with variable method and timing of CSF diversion and were subject to surgeon bias. No significant differences between cohorts were observed with regard to age, sex, tumor grade or histology, metastatic status, or extent of resection. The cumulative failure rate of ETV was 21%, whereas that of VPS surgery was 29% (p = 0.105). The median time to failure was earlier for ETV than for VPS surgery (0.82 [IQR 0.2-1.8] vs 4.7 months [IQR 0.3-5.7], p = 0.03). Initially the ETV survival curve dropped sharply and then stabilized around 2 months. The VPS curve fell gradually but eventually crossed below the ETV curve at 5.7 months. Overall, a significant survival advantage was not demonstrated for one procedure over the other (p = 0.21, log-rank). However, postoperative complications were higher following VPS (31%) than ETV (17%) (p = 0.012). CONCLUSIONS ETV failure occurred sooner than VPS failure, but long-term treatment durability may be higher for ETV. Complications occurred more commonly with VPS than with ETV. Limited clinical conclusions are drawn using this methodology; the optimal treatment for PFBT-related hydrocephalus warrants investigation through prospective studies.

Plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite OSI-420.

PubMed

Broniscer, Alberto; Panetta, John C; O'Shaughnessy, Melinda; Fraga, Charles; Bai, Feng; Krasin, Matthew J; Gajjar, Amar; Stewart, Clinton F

2007-03-01

To report cerebrospinal fluid (CSF) penetration of erlotinib and its metabolite OSI-420. Pharmacokinetic measurements were done in plasma (days 1, 2, 3, and 8 of therapy) and, concurrently, in plasma and CSF (before and at 1, 2, 4, 8, and 24 h after dose on day 34 of therapy) in an 8-year-old patient diagnosed with glioblastoma who received local irradiation and oral erlotinib in a phase I protocol. CSF samples were collected from a ventriculoperitoneal shunt, which was externalized because of infection. Erlotinib concentrations were determined by liquid chromatography/mass spectrometry. CSF penetration of erlotinib and OSI-420 were estimated by a compartmental model and by calculating the ratio of CSF to plasma 24-h area under concentration-time curve (AUC(0-24)). This patient was assigned to receive erlotinib at a dose level of 70 mg/m(2), but the actual daily dose was 75 mg (78 mg/m(2)). Erlotinib and OSI-420 plasma pharmacokinetic variables on days 8 and 34 overlapped to suggest that steady state had been reached. Whereas erlotinib and OSI-420 AUC(0-24) in plasma on day 34 were 30,365 and 2,527 ng h/mL, respectively, the correspondent AUC(0-24) in the CSF were 2,129 and 240 ng h/mL, respectively. Erlotinib and OSI-420 CSF penetration were 7% and approximately 9%, respectively, using both estimate methods. The maximum steady-state CSF concentration of erlotinib was approximately 130 ng/mL (325 nmol/L). The plasma pharmacokinetics of erlotinib in this child overlapped with results described in adults. Oral administration of erlotinib achieves CSF concentrations comparable with those active against several cancer cell lines in preclinical models.

Surgical management of bacterial meningitis.

PubMed Central

Humphreys, R. P.

1975-01-01

A variety of associated lesions may require the neurosurgeon's assistance in the management of bacterial meningitis. As treatment of this infection of the central nervous system proceeds, the surgeon will have to decide about the concurrent or subsequent operative treatment of congenital dysraphic states, paraneural infections, compound fractures or penetrating wounds of thecranium or spine, or infected bypass shunts for cerebrospinal fluid (CSF). In patients with intractable meningitic infections the surgeon may have to insert a ventricular drainage-irrigation system to permit adequate perfusion of the CSF pathways with antibiotic. Hydrocephalus or subdural effusions complicating meningitis may bring the patient to the surgeon long after the infection has been cured. This paper examines these problems and outlines the current principles of management. Images FIG. 1 FIG. 2 PMID:1098760

Supraorbital Keyhole Microsurgical Fenestration of Symptomatic Temporal Arachnoid Cysts in Children: Advantages and Limitations.

PubMed

Elkheshin, Sherif; Soliman, Ahmed

2017-01-01

To investigate the impact of endoscope-assisted microsurgical fenestration on temporal arachnoid cysts, and to determine the advantages and limitations of the technique. Twenty-five children with symptomatic temporal arachnoid cysts were operated via eyebrow supraorbital keyhole microsurgical fenestration targeting the medial cyst wall. Preoperative magnetic resonance imaging (MRI) of the brain was done for all patients. Preoperative clinical presentation of the patients included headache (80%), nausea & vomiting (64%), drug resistant epilepsy (52%), macrocephaly (12%) papilledema (28%), motor weakness in the form of right-sided hemiparesis (12%) and cranial nerve palsy. Postoperative complete subsidence of headache was noted in 50%, while 20% remained unchanged. Drug resistant epilepsy improved in 69% of the patients. Postoperative MRI showed initial decrease in cyst volume as early as 3 months, only in a range of 5-12% volume reduction, and the late follow-up done at 6 and 18 months continued to show further reduction reported to be significant (p < 0.001). Transient subgaleal cerebrospinal fluid (CSF) collection was the most common complication (20%). Only 1 patient experienced CSF leak mandating cysto-peritoneal shunting. Conclusıon: Eyebrow supraorbital keyhole microsurgical fenestration for temporal arachnoid cysts can be performed with a fairly low risk of complications and yields a favorable improvement in clinical and neuroimaging outcomes.

Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices.

PubMed Central

Christensen, G D; Simpson, W A; Younger, J J; Baddour, L M; Barrett, F F; Melton, D M; Beachey, E H

1985-01-01

The adherence of coagulase-negative staphylococci to smooth surfaces was assayed by measuring the optical densities of stained bacterial films adherent to the floors of plastic tissue culture plates. The optical densities correlated with the weight of the adherent bacterial film (r = 0.906; P less than 0.01). The measurements also agreed with visual assessments of bacterial adherence to culture tubes, microtiter plates, and tissue culture plates. Selected clinical strains were passed through a mouse model for foreign body infections and a rat model for catheter-induced endocarditis. The adherence measurements of animal passed strains remained the same as those of the laboratory-maintained parent strain. Spectrophotometric classification of coagulase-negative staphylococci into nonadherent and adherent categories according to these measurements had a sensitivity, specificity, and accuracy of 90.6, 80.8, and 88.4%, respectively. We examined a previously described collection of 127 strains of coagulase-negative staphylococci isolated from an outbreak of intravascular catheter-associated sepsis; strains associated with sepsis were more adherent than blood culture contaminants and cutaneous strains (P less than 0.001). We also examined a collection of 84 strains isolated from pediatric patients with cerebrospinal fluid (CSF) shunts; once again, pathogenic strains were more adherent than were CSF contaminants (P less than 0.01). Finally, we measured the adherence of seven endocarditis strains. As opposed to strains associated with intravascular catheters and CSF shunts, endocarditis strains were less adherent than were saprophytic strains of coagulase-negative staphylococci. The optical densities of bacterial films adherent to plastic tissue culture plates serve as a quantitative model for the study of the adherence of coagulase-negative staphylococci to medical devices, a process which may be important in the pathogenesis of foreign body infections. Images PMID:3905855

Outcome prediction of third ventriculostomy: a proposed hydrocephalus grading system.

PubMed

Kehler, U; Regelsberger, J; Gliemroth, J; Westphal, M

2006-08-01

An important factor in making a recommendation for different treatment modalities in hydrocephalus patients (VP shunt versus endoscopic third ventriculostomy) is the definition of the underlying pathology which determines the prognosis/outcome of the surgical procedure. Third ventriculostomies (3rd VS) are successful mainly in obstructive hydrocephalus but also in some subtypes of communicating hydrocephalus. A simple, easily applicable grading system that is designed to predict the outcome of 3rd VS is proposed. The hydrocephalus is graded on the basis of the extent of downward bulging of the floor of the third ventricle, which reflects the pressure gradient between the 3rd ventricle and the basal cisterns, presence of directly visualised CSF pathway obstruction in MRI, and the progression of the clinical symptoms resulting in five different grades. In this proposed grading system, grade 1 hydrocephalus subtype shows no downward bulged floor of the 3rd ventricle, no obstruction of the CSF pathway, and no progressive symptoms of hydrocephalus. There is no indication for 3rd VS. Grades 2 to 4 show different combinations of the described parameters. Grade 5 subtype shows a markedly downward bulged floor of the 3rd ventricle and direct detection of the CSF pathway obstruction (i.e., aqueductal stenosis) with progressive clinical deterioration. Retrospective application of this grading scheme to a series of 72 3rd VS has demonstrated a high correlation with the outcome: The success rate in grade 3 reached 40%, in grade 4: 58%, and in grade 5: 95%. This standardised grading system predicts the outcome of 3rd VS and helps in decision making for 3rd VS versus VP shunting.

Cerebrospinal fluid circulation and hydrocephalus.

PubMed

Leinonen, Ville; Vanninen, Ritva; Rauramaa, Tuomas

2017-01-01

Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorption of cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include various brain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarachnoid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment, with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicating HC. Another clinically relevant classification is acute and chronic; the most frequent chronic form is idiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according to the study population and classification used. The incidence of congenital HC is approximately 0.4-0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radiologically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegenerative diseases may be ambiguous. There are no known specific microscopic findings of HC but a systematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic factors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of ICP monitoring in patients with persistent cerebrospinal fluid leak following spinal surgery: a case series.

PubMed

Craven, Claudia; Toma, Ahmed K; Khan, Akbar A; Watkins, Laurence D

2016-09-01

Cerebrospinal fluid (CSF) leak following spinal surgery is a relatively common surgical complication. A disturbance in the underlying CSF dynamics could be the causative factor in a small group of patients with refractory CSF leaks that require multiple surgical repairs and prolonged hospital admission. A retrospective case series of patients with persistent post spinal surgery CSF leak referred to the hydrocephalus service for continuous intracranial pressure (ICP) monitoring. Patients' notes were reviewed for medical history, ICP data, radiological data, and subsequent management and outcome. Five patients (two males/three females, mean age, 35.4 years) were referred for ICP monitoring over a 12-month period. These patients had prolonged CSF leak despite multiple repair attempts 252 ± 454 days (mean ± SD). On ICP monitoring, all five patients had abnormal results, with the mean ICP 8.95 ± 4.41 mmHg. Four had abnormal pulse amplitudes, mean 6.15 mmHg ± 1.22 mmHg. All five patients underwent an intervention. Three patients underwent insertion of ventriculoperitoneal (VP) shunts. One patient had venous sinus stent insertion and one patient underwent medical management with acetazolamide. All five of the patients' CSF leak resolved post intervention. The mean time to resolution of CSF leak post intervention was 10.8  ± 12.9 days. Abnormal cerebrospinal fluid dynamics could be the underlying factor in patients with a persistent and treatment-refractory CSF leak post spinal surgery. Treatments aimed at lowering ICP may be beneficial in this group of patients. Whether abnormal pressure and dynamics represent a pre-existing abnormality or is induced by spinal surgery should be a subject of further study.

Endoscopic Third Ventriculostomy Instead of Shunt Revision in Children Younger Than 3 Years of Age.

PubMed

Zhao, Rui; Shi, Wei; Yang, Haowei; Li, Hao

2016-04-01

Endoscopic third ventriculostomy (ETV) is a valuable option in the treatment of shunt failure, but no clinical data exist for young children. The aim of this study was to elucidate the role of ETV in patients younger than 3 years of age with shunt malfunction. A cohort of 37 patients younger than 3 years of age with shunt malfunction underwent ETV instead of shunt revision. Patients' preoperative condition and medical history were studied to determine the impact of a number of variables on outcome. The Fisher exact test was used to assess differences among groups. Median age at ETV was 21.6 months (8-36 months). Diagnosis was obstructive hydrocephalus in 24 patients and communicating hydrocephalus in 13. Median age at initial shunt placement was 3.2 months (10 days to 30 months). The etiology of shunt malfunction was obstruction (n = 27) or infection (n = 10). Overall ETV failure rate was 40.5% (15/37). Patients whose age at initial shunt placement was <6 months and/or who had a preterm birth history had higher relative rates of ETV failure. Other variables, including type of hydrocephalus, interval between initial shunt placement and ETV, history of intraventricular bleeding and/or infection, and etiology of shunt malfunction, did not significantly affect the final outcome. Patients younger than 3 years with obstructive or communicating hydrocephalus may benefit from ETV in the event of shunt malfunction and have about a 60% probability of becoming shunt free. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebrospinal fluid pulse pressure amplitude during lumbar infusion in idiopathic normal pressure hydrocephalus can predict response to shunting

PubMed Central

2010-01-01

Background We have previously seen that idiopathic normal pressure hydrocephalus (iNPH) patients having elevated intracranial pressure (ICP) pulse amplitude consistently respond to shunt surgery. In this study we explored how the cerebrospinal fluid pressure (CSFP) pulse amplitude determined during lumbar infusion testing, correlates with ICP pulse amplitude determined during over-night ICP monitoring and with response to shunt surgery. Our goal was to establish a more reliable screening procedure for selecting iNPH patients for shunt surgery using lumbar intrathecal infusion. Methods The study population consisted of all iNPH patients undergoing both diagnostic lumbar infusion testing and continuous over-night ICP monitoring during the period 2002-2007. The severity of iNPH was assessed using our NPH grading scale before surgery and 12 months after shunting. The CSFP pulse was characterized from the amplitude of single pressure waves. Results Totally 62 iNPH patients were included, 45 of them underwent shunt surgery, in whom 78% were shunt responders. Among the 45 shunted patients, resistance to CSF outflow (Rout) was elevated (≥ 12 mmHg/ml/min) in 44. The ICP pulse amplitude recorded over-night was elevated (i.e. mean ICP wave amplitude ≥ 4 mmHg) in 68% of patients; 92% of these were shunt responders. In those with elevated overnight ICP pulse amplitude, we found also elevated CSFP pulse amplitude recorded during lumbar infusion testing, both during the opening phase following lumbar puncture and during a standardized period of lumbar infusion (15 ml Ringer over 10 min). The clinical response to shunting after 1 year strongly associated with the over-night ICP pulse amplitude, and also with the pulsatile CSFP during the period of lumbar infusion. Elevated CSFP pulse amplitude during lumbar infusion thus predicted shunt response with sensitivity of 88 and specificity of 60 (positive and negative predictive values of 89 and 60, respectively). Conclusions In iNPH patients, shunt response can be anticipated in 9/10 patients with elevated overnight ICP pulse amplitude, while in only 1/10 with low ICP pulse amplitude. Additionally, the CSFP pulse amplitude during lumbar infusion testing was elevated in patients with elevated over-night ICP pulse amplitude. In particular, measurement of CSFP pulse amplitude during a standardized infusion of 15 ml Ringer over 10 min was useful in predicting response to shunt surgery and can be used as a screening procedure for selection of iNPH patients for shunting. PMID:20205911

Noninvasive measurement of cerebrospinal fluid flow using an ultrasonic transit time flow sensor: a preliminary study.

PubMed

Pennell, Thomas; Yi, Juneyoung L; Kaufman, Bruce A; Krishnamurthy, Satish

2016-03-01

OBJECT Mechanical failure-which is the primary cause of CSF shunt malfunction-is not readily diagnosed, and the specific reasons for mechanical failure are not easily discerned. Prior attempts to measure CSF flow noninvasively have lacked the ability to either quantitatively or qualitatively obtain data. To address these needs, this preliminary study evaluates an ultrasonic transit time flow sensor in pediatric and adult patients with external ventricular drains (EVDs). One goal was to confirm the stated accuracy of the sensor in a clinical setting. A second goal was to observe the sensor's capability to record real-time continuous CSF flow. The final goal was to observe recordings during instances of flow blockage or lack of flow in order to determine the sensor's ability to identify these changes. METHODS A total of 5 pediatric and 11 adult patients who had received EVDs for the treatment of hydrocephalus were studied in a hospital setting. The primary EVD was connected to a secondary study EVD that contained a fluid-filled pressure transducer and an in-line transit time flow sensor. Comparisons were made between the weight of the drainage bag and the flow measured via the sensor in order to confirm its accuracy. Data from the pressure transducer and the flow sensor were recorded continuously at 100 Hz for a period of 24 hours by a data acquisition system, while the hourly CSF flow into the drip chamber was recorded manually. Changes in the patient's neurological status and their time points were noted. RESULTS The flow sensor demonstrated a proven accuracy of ± 15% or ± 2 ml/hr. The flow sensor allowed real-time continuous flow waveform data recordings. Dynamic analysis of CSF flow waveforms allowed the calculation of the pressure-volume index. Lastly, the sensor was able to diagnose a blocked catheter and distinguish between the blockage and lack of flow. CONCLUSIONS The Transonic flow sensor accurately measures CSF output within ± 15% or ± 2 ml/hr, diagnoses the blockage or lack of flow, and records real-time continuous flow data in patients with EVDs. Calculations of a wide variety of diagnostic parameters can be made from the waveform recordings, including resistance and compliance of the ventricular catheters and the compliance of the brain. The sensor's clinical applications may be of particular importance to the noninvasive diagnosis of shunt malfunctions with the development of an implantable device.

MRI safety of a programmable shunt assistant at 3 and 7 Tesla.

PubMed

Mirzayan, M Javad; Klinge, Petra M; Samii, Madjid; Goetz, Friedrich; Krauss, Joachim K

2012-06-01

Several new shunt technologies have been developed to optimize hydrocephalus treatment within the past few years. Overdrainage, however, still remains an unresolved problem. One new technology which may reduce the frequency of this complication is the use of a programmable shunt assistant (proSA). Inactive in a horizontal position, it impedes CSF flow in a vertical position according to a prescribed pressure level ranging from 0 to 40 cm H(2)O. We exposed the proSA valve in an ex vivo protocol to MR systems operating at 3 and 7 Tesla to investigate its MRI safety. Following 3 Tesla exposure, no changes in valve settings were noted. Adjustment to any pressure level was possible thereafter. The mean deflection angle was 23 ± 3°. After exposure to 7 Tesla, however, there were unintended pressure changes, and the mechanism for further adjustment of the valves even disintegrated. According to the results of this study, proSA is safe with heteropolar vertical magnet alignment at 3 Tesla. Following 7 Tesla exposure, the valves lost their functional capability.

Relative Position of the Third Characteristic Peak of the Intracranial Pressure Pulse Waveform Morphology Differentiates Normal-Pressure Hydrocephalus Shunt Responders and Nonresponders.

PubMed

Hamilton, Robert; Fuller, Jennifer; Baldwin, Kevin; Vespa, Paul; Hu, Xiao; Bergsneider, Marvin

2016-01-01

The diversion of cerebrospinal fluid (CSF) remains the principal treatment option for patients with normal-pressure hydrocephalus (NPH). External lumbar drain (ELD) and overnight intracranial pressure (ICP) monitoring are popular prognostic tests for differentiating which patients will benefit from shunting. Using the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm to extract morphological metrics from the overnight ICP signal, we hypothesize that changes in the third peak of the ICP pulse pressure waveform can be used to differentiate ELD responders and nonresponders. Our study involved 66 patients (72.2 ± 9.8 years) undergoing evaluation for possible NPH, which included overnight ICP monitoring and ELD. ELD outcome was based on clinical notes and divided into nonresponders and responders. MOCAIP was used to extract mean ICP, ICP wave amplitude (waveAmp), and a metric derived to study P3 elevation (P3ratio). Of the 66 patients, 7 were classified as nonresponders and 25 as significant responders. The mean ICP and waveAmp did not vary significantly (p = 0.19 and p = 0.41) between the outcome groups; however, the P3ratio did show a significant difference (p = 0.04). Initial results suggest that the P3ratio might be used as a prognostic indicator for ELD outcome.

[Suprasellar arachnoid cyst--report of a case (author's transl)].

PubMed

Takahashi, T; Kawai, S; Kaminoh, T; Hiramatsu, K; Maekawa, M; Yuasa, T; Miyamoto, N; Hattori, Y

1982-04-01

A 4-year-old boy with suprasellar arachnoid cyst was reported. At the age of 30-month-old his aunt was aware of his squint. During the observation by ophthalmologists from the age of 1y. to 3y., enlargement of the head and impairment of the visual acuity were manifested. Cranial CT scan revealed the enlargement of the ventricular system and a round low density area located superior to the sella. Absorption coefficient of the lesion was similar to that of the cerebrospinal fluid. No abnormal contrast enhancement was seen. Examination revealed the head circumference of 53.3 cm larger than doubled standard deviation, the right external strabismus, impaired vision (R:0.03, L:0.3) and optic atrophy but no other neurological signs. Cerebral angiography showed suprasellar mass lesion. After the ventriculography with water-soluble contrast medium, V-P shunt operation was performed and then the patient was transferred to the CT room. CSF enhanced CT scan showed no communication between the ventricles and the cyst. By frontotemporal approach, microsurgical removal of the cystwall was performed and the histological diagnosis was arachnoid membrane. Several days after the operation, bilateral subdural effusion was seen on CT scan and was treated with bilateral S-P shunt and the removal of V-P shunt. Follow up CT scan disclosed the disappearance of the subdural effusion and the suprasellar cyst. The visual acuity was improved well and the endocrinological study was normal. Analysis of the 45 reported cases of suprasellar arachnoid cyst suggested that direct removal of the cyst wall is better than the V-P shunt operation and the cyst shunting is advisable for repeat recurrence of the cyst. Removal of the ventricular shunting system may be effective for the prevention of the subdural effusion as a complication after direct operation.

A computational fluid dynamics simulation framework for ventricular catheter design optimization.

PubMed

Weisenberg, Sofy H; TerMaath, Stephanie C; Barbier, Charlotte N; Hill, Judith C; Killeffer, James A

2017-11-10

OBJECTIVE Cerebrospinal fluid (CSF) shunts are the primary treatment for patients suffering from hydrocephalus. While proven effective in symptom relief, these shunt systems are plagued by high failure rates and often require repeated revision surgeries to replace malfunctioning components. One of the leading causes of CSF shunt failure is obstruction of the ventricular catheter by aggregations of cells, proteins, blood clots, or fronds of choroid plexus that occlude the catheter's small inlet holes or even the full internal catheter lumen. Such obstructions can disrupt CSF diversion out of the ventricular system or impede it entirely. Previous studies have suggested that altering the catheter's fluid dynamics may help to reduce the likelihood of complete ventricular catheter failure caused by obstruction. However, systematic correlation between a ventricular catheter's design parameters and its performance, specifically its likelihood to become occluded, still remains unknown. Therefore, an automated, open-source computational fluid dynamics (CFD) simulation framework was developed for use in the medical community to determine optimized ventricular catheter designs and to rapidly explore parameter influence for a given flow objective. METHODS The computational framework was developed by coupling a 3D CFD solver and an iterative optimization algorithm and was implemented in a high-performance computing environment. The capabilities of the framework were demonstrated by computing an optimized ventricular catheter design that provides uniform flow rates through the catheter's inlet holes, a common design objective in the literature. The baseline computational model was validated using 3D nuclear imaging to provide flow velocities at the inlet holes and through the catheter. RESULTS The optimized catheter design achieved through use of the automated simulation framework improved significantly on previous attempts to reach a uniform inlet flow rate distribution using the standard catheter hole configuration as a baseline. While the standard ventricular catheter design featuring uniform inlet hole diameters and hole spacing has a standard deviation of 14.27% for the inlet flow rates, the optimized design has a standard deviation of 0.30%. CONCLUSIONS This customizable framework, paired with high-performance computing, provides a rapid method of design testing to solve complex flow problems. While a relatively simplified ventricular catheter model was used to demonstrate the framework, the computational approach is applicable to any baseline catheter model, and it is easily adapted to optimize catheters for the unique needs of different patients as well as for other fluid-based medical devices.

Intracranial pressure monitoring in pediatric and adult patients with hydrocephalus and tentative shunt failure: a single-center experience over 10 years in 146 patients.

PubMed

Sæhle, Terje; Eide, Per Kristian

2015-05-01

OBJECT In patients with hydrocephalus and shunts, lasting symptoms such as headache and dizziness may be indicative of shunt failure, which may necessitate shunt revision. In cases of doubt, the authors monitor intracranial pressure (ICP) to determine the presence of over- or underdrainage of CSF to tailor management. In this study, the authors reviewed their experience of ICP monitoring in shunt failure. The aims of the study were to identify the complications and impact of ICP monitoring, as well as to determine the mean ICP and characteristics of the cardiac-induced ICP waves in pediatric versus adult over- and underdrainage. METHODS The study population included all pediatric and adult patients with hydrocephalus and shunts undergoing diagnostic ICP monitoring for tentative shunt failure during the 10-year period from 2002 to 2011. The patients were allocated into 3 groups depending on how they were managed following ICP monitoring: no drainage failure, overdrainage, or underdrainage. While patients with no drainage failure were managed conservatively without further actions, over- or underdrainage cases were managed with shunt revision or shunt valve adjustment. The ICP and ICP wave scores were determined from the continuous ICP waveforms. RESULTS The study population included 71 pediatric and 75 adult patients. There were no major complications related to ICP monitoring, but 1 patient was treated for a postoperative superficial wound infection and another experienced a minor bleed at the tip of the ICP sensor. Following ICP monitoring, shunt revision was performed in 74 (51%) of 146 patients, while valve adjustment was conducted in 17 (12%) and conservative measures without any actions in 55 (38%). Overdrainage was characterized by a higher percentage of episodes with negative mean ICP less than -5 to -10 mm Hg. The ICP wave scores, in particular the mean ICP wave amplitude (MWA), best differentiated underdrainage. Neither mean ICP nor MWA levels showed any significant association with age. CONCLUSIONS In this cohort of pediatric and adult patients with hydrocephalus and tentative shunt failure, the risk of ICP monitoring was very low, and helped the authors avoid shunt revision in 49% of the patients. Mean ICP best differentiated overdrainage, which was characterized by a higher percentage of episodes with negative mean ICP less than -5 to -10 mm Hg. Underdrainage was best characterized by elevated MWA values, indicative of impaired intracranial compliance.

Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

PubMed

Bech, R A; Waldemar, G; Gjerris, F; Klinken, L; Juhler, M

1999-01-01

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

Dementia paralytica: deterioration from communicating hydrocephalus.

PubMed Central

Giménez-Roldán, S; Benito, C; Martin, M

1979-01-01

Five patients suffering from dementia paralytica who failed to improve or deteriorated after one or several high dosage courses of penicillin, had pneumoencephalographic patterns suggesting communicating hydrocephalus. Measurements of the ventricular index, ratio of cella media to width of the temporal horn, and the callosal angle differed from that in seven cases of dementia paralytica with associated cerebral atrophy. An isotope cisternogram in three cases with communicating hydrocephalus further confirmed a blockage of the cerebrospinal fluid (CSF) at the parasagittal subarachnoid space. Three patients exhibited the full syndrome of gait apraxia, incontinence, and pyramidal tract signs associated with a severe degree of dementia. Shunting of the CSF in three cases was followed by immediate improvement in two, one in a longlasting way. No active parenchymal inflammation was observed in any of three brain biopsy samples taken during surgery, except for leptomeningeal fibrosis in one. Chronic leptomeningitis in dementia paralytica may impair subarachnoid CSF absorption with subsequent communicating hydrocephalus. Progression or inadequate responses after therapeutic dose of penicillin in dementia paralytica should prompt investigation for this complication as an alternative, effective treatment could be offered. Images PMID:469557

Short ORF-Dependent Ribosome Shunting Operates in an RNA Picorna-Like Virus and a DNA Pararetrovirus that Cause Rice Tungro Disease

PubMed Central

Pooggin, Mikhail M.; Rajeswaran, Rajendran; Schepetilnikov, Mikhail V.; Ryabova, Lyubov A.

2012-01-01

Rice tungro disease is caused by synergistic interaction of an RNA picorna-like virus Rice tungro spherical virus (RTSV) and a DNA pararetrovirus Rice tungro bacilliform virus (RTBV). It is spread by insects owing to an RTSV-encoded transmission factor. RTBV has evolved a ribosome shunt mechanism to initiate translation of its pregenomic RNA having a long and highly structured leader. We found that a long leader of RTSV genomic RNA remarkably resembles the RTBV leader: both contain several short ORFs (sORFs) and potentially fold into a large stem-loop structure with the first sORF terminating in front of the stem basal helix. Using translation assays in rice protoplasts and wheat germ extracts, we show that, like in RTBV, both initiation and proper termination of the first sORF translation in front of the stem are required for shunt-mediated translation of a reporter ORF placed downstream of the RTSV leader. The base pairing that forms the basal helix is required for shunting, but its sequence can be varied. Shunt efficiency in RTSV is lower than in RTBV. But in addition to shunting the RTSV leader sequence allows relatively efficient linear ribosome migration, which also contributes to translation initiation downstream of the leader. We conclude that RTSV and RTBV have developed a similar, sORF-dependent shunt mechanism possibly to adapt to the host translation system and/or coordinate their life cycles. Given that sORF-dependent shunting also operates in a pararetrovirus Cauliflower mosaic virus and likely in other pararetroviruses that possess a conserved shunt configuration in their leaders it is tempting to propose that RTSV may have acquired shunt cis-elements from RTBV during their co-existence. PMID:22396650

Endoscopic cystoventriculostomy and ventriculocysternostomy using a recently developed 2.0-micron fiber-guided high-power diode-pumped solid state laser in children with hydrocephalus

NASA Astrophysics Data System (ADS)

Ludwig, Hans C.; Kruschat, Thomas; Knobloch, Torsten; Rostasy, Kevin; Buchfelder, Michael

2005-04-01

Preterm infants have a high incidence of post hemorrhagic or post infectious hydrocephalus often associated with ventricular or arachnoic cysts which carry a high risk of entrapment of cerebrospinal fluid (CSF). In these cases fenestration and opening of windows within the separating membranes are neurosurgical options. Although Nd:YAG- and diode-lasers have already been used in neuroendoscopic procedures, neurosurgeons avoid the use of high energy lasers in proximity to vital structures because of potential side effects. We have used a recently developed diode pumped solid state (DPSS) laser emitting light at a wavelength of 2.0 μm (Revolix TM LISA laser products, Katlenburg, Germany), which can be delivered through silica fibres towards endoscopic targets. From July 2002 until June 2004 fourteen endoscopic procedures in 12 consecutive patients (age 3 months to 12 years old) were performed. Most children suffered from complex post hemorrhagic and post infectious hydrocephalus, in whom ventriculoperitoneal shunt devices failed to restore a CSF equilibrium due to entrapment of CSF pathways by the cysts. We used two different endoscopes, a 6 mm Neuroendoscope (Braun Aesculap, Melsungen, Germany; a 4 mm miniature Neuroscope (Storz, Tuttlingen, Germany). The endoscopes were connected to a standard camera and TV monitor, the laser energy was introduced through a 365 μm core diameter bare ended silica fibre (PercuFib, LISA laser products, Katlenburg, Germany) through the endoscope"s working channel. The continuous wave laser was operated at power levels from 5 to 15 Watt in continuous and chopped mode. The frequency of the laser in chopped mode was varied between 5 and 20 Hz. All patients tolerated the procedure well. No immediate or long term side effects were noted. In 3 patients with cystic compression of the 4th ventricle, insertion of a shunt device could be avoided. The authors conclude that the use of the new RevolixTM laser enables safe and effective procedures in neuroendoscopy.

Ventriculostomy for acute hydrocephalus in critically ill patients on the ICU--outcome analysis of two different procedures.

PubMed

Schödel, Petra; Proescholdt, Martin; Brawanski, Alexander; Bele, Sylvia; Schebesch, Karl-Michael

2012-04-01

Burr-hole trephine and insertion of an external ventricular drainage (EVD) is a common procedure in neurosurgical practice. In critically ill patients, the transport to the operating room, OR represents a major risk. Thus, the burr-hole trephine and implantation of an EVD is frequently performed on the Intensive Care Unit (ICU). Since 2004, we have applied two different procedures: the conventional method with a mechanical compressed air or an electric drill, and an alternative method with a manual twist drill, including fixation of the EVD in a skull screw (Bolt Kit, Raumedic AG, Germany). This study was designed to evaluate the outcome of both surgical procedures. In this retrospective analysis we included 166 consecutive patients with acute hydrocephalus due to intracranial hemorrhage that had been operated at our neurosurgical ICU in a six years interval. We reviewed the charts for gender and age, kind of surgical procedure, cerebrospinal fluid (CSF)-infections, duration of drainage, attempts of insertions, wound infections, misplacement rate, post-surgical hemorrhages, revisions, comorbidities and shunt-dependency. In 122 patients we applied the Bolt Kit System, in 44 patients the conventional method was performed. We found a significantly lower rate of CSF-infections and significantly fewer attempts of insertions in the Bolt Kit group (p = 0.002 and p = 0.001, respectively). The rate of wound infections, misplacement, revisions, shunt-dependency and the post-surgical hemorrhages did not differ significantly. Our data indicate that the manual drill and the skull screw are safe and feasible tools in the treatment of acute hydrocephalus. Presumably, the direct skin contact is causative for the higher rate of CSF-infections when the conventional method is performed. The skull screw guides the EVD into the ventricle without skin contact. The lower number of insertions needed may be due to the fact that the skull screw allows just one trajectory for the insertion of the EVD.

Compensatory parameters of intracranial space in giant hydrocephalus.

PubMed

Cieślicki, Krzysztof; Czepko, Ryszard

2009-01-01

The main goal of the present study is to examine compensatory parameters of intracranial space in giant hydrocephalus. We also assess the early and late outcome and analyse complications in shunted cases. Nine cases of giant hydrocephalus characterised by the value of Evans ratio > 0.5, ventricular index > 1.5, and the width of the third ventricle > 20 mm were considered. Using the lumbar infusion test and developed software we analysed the intracranial compensatory parameters typical for hydrocephalus. Based on the Marmarou model, the method depended on a repeated search for the best fitting curve corresponding to the progress of the test was used. Eight out of nine patients were therefore shunted. Patients were followed up for 9 months. Five out of eight shunted patients undoubtedly improved in a few days after surgery (62%). Complications (subdural hygromas/haematomas and intracerebral haematoma) developed in 5 (62%) cases in longer follow-up. A definite improvement was noted in 4 out of 8 operated cases (50%). To get the stable values of compensatory parameters, the duration of the infusion test must at least double the inflexion time of the test curve. All but one considered cases of giant hydrocephalus were characterized by lack of intracranial space reserve, significantly reduced rate of CSF secretion and by various degrees of elevated value of the resistance to outflow. Due to the significant number of complications and uncertain long-term improvement, great caution in decision making for shunting has to be taken.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

Hydrodynamics of the Certas™ programmable valve for the treatment of hydrocephalus

PubMed Central

2012-01-01

Background The new Certas™ shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional “Virtual Off” setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the “Virtual Off” setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the Certas™ shunt. Methods Six new Certas™ shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined. Results For settings 1–7 the measured opening pressure range was 26 to 247 mmH2O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For setting 8 (“Virtual Off”) the measured mean opening pressure was 494 ± 34 mmH2O (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 μl/s/kPa). Conclusions The six shunts had similar characteristics and closely matched the manufacturer’s specifications for opening pressure at settings 1–7. The opening pressure for the “Virtual Off” setting was nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer’s specification of “>400” and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients. PMID:22643114

Hypoglycorrhachia in Adults with Community-Acquired Meningitis: Etiologies and Prognostic Significance

PubMed Central

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-01-01

Study objectives Hypoglycorrhachia (CSF glucose < 45mg/dL) has been identified as a prognostic factor in patients with meningitis. We analyzed the differential diagnosis of hypoglycorrhachia and its clinical significance. Methods Retrospective study of 620 adult patients with community acquired meningitis [CSF WBC >5 cells/mm3, absence of a CSF shunt or recent neurosurgical procedure (< 1 month)] at 8 Memorial Hermann Hospitals in Houston, TX from January, 2005 to December, 2010. An adverse clinical outcome was defined as a Glasgow outcome scale of 4 or less. Results Out of 620 patients with meningitis, 116 (19%) had hypoglycorrachia. Etiologies of hypoglycorrhachia were idiopathic (40), bacterial (27), cryptococcal (26), viral (15), and tuberculous (4). Patients with hypoglycorrachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status and focal neurological deficits compared to those patients without hypoglycorrachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions and abnormal cranial imaging (p<005). Furthermore, patients with hypoglycorrachia had more adverse clinical outcomes [26 out of 116 (22.4%) vs. 45 out of 504 (8.9%)] (p< 0.001). Conclusion Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. PMID:26299186

Neck swelling due to skull base (pseudo)meningocele protruding through a congenital skull base bone defect: a case report.

PubMed

Sharma, Rajeev; Singh, Bhoopendra; Kedia, Shweta; Laythalling, Rajinder Kumar

2017-02-01

Meningocele is defined as a protrusion of the meninges through an opening in the skull or spinal column, forming a bulge or sac filled with cerebrospinal fluid. A pseudomeningocele is defined as a cerebrospinal fluid (CSF) collection formed due to escape of CSF through a dural defect with trapping of CSF into the surrounding soft tissues. We herby report rare occurrence of a large (pseudo)meningocele in a young patient with congenital skull base defect presenting as upper lateral neck swelling. We present the case of a 17-year-old boy who had painless progressive swelling right side of the upper neck without any history of meningitis or CSF leak. He had a history of undergoing cranioplasty using steel plates for nontraumatic boggy swelling right parieto-occipital region at the age of 5 years at another hospital. Clinical examination showed painless swelling right side of the upper neck, with positive cough impulse and transillumination. CT head with cisternography showed a large right skull base defect through which a large pseudomeningocele was herniating, thus producing upper neck swelling and compressing oral cavity. The neck swelling and intraoral bulge reduced in size after the coperitoneal shunt. Differential diagnosis of (pseudo)meningocele should be considered while evaluating a painless progressive upper neck swelling having cough impulse and transillumination in a young patient.

Classification of hydrocephalus: critical analysis of classification categories and advantages of "Multi-categorical Hydrocephalus Classification" (Mc HC).

PubMed

Oi, Shizuo

2011-10-01

Hydrocephalus is a complex pathophysiology with disturbed cerebrospinal fluid (CSF) circulation. There are numerous numbers of classification trials published focusing on various criteria, such as associated anomalies/underlying lesions, CSF circulation/intracranial pressure patterns, clinical features, and other categories. However, no definitive classification exists comprehensively to cover the variety of these aspects. The new classification of hydrocephalus, "Multi-categorical Hydrocephalus Classification" (Mc HC), was invented and developed to cover the entire aspects of hydrocephalus with all considerable classification items and categories. Ten categories include "Mc HC" category I: onset (age, phase), II: cause, III: underlying lesion, IV: symptomatology, V: pathophysiology 1-CSF circulation, VI: pathophysiology 2-ICP dynamics, VII: chronology, VII: post-shunt, VIII: post-endoscopic third ventriculostomy, and X: others. From a 100-year search of publication related to the classification of hydrocephalus, 14 representative publications were reviewed and divided into the 10 categories. The Baumkuchen classification graph made from the round o'clock classification demonstrated the historical tendency of deviation to the categories in pathophysiology, either CSF or ICP dynamics. In the preliminary clinical application, it was concluded that "Mc HC" is extremely effective in expressing the individual state with various categories in the past and present condition or among the compatible cases of hydrocephalus along with the possible chronological change in the future.

Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid.

PubMed

Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs, Jonathan G; Mehta, Ankit I; Linninger, Andreas

2016-09-01

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Reversible grasp reflexes in normal pressure hydrocephalus.

PubMed

Thomas, Rhys H; Bennetto, Luke; Silva, Mark T

2009-05-01

We present two cases of normal pressure hydrocephalus in combination with grasp reflexes. In both cases the grasp reflexes disappeared following high volume cerebrospinal fluid removal. In one of the cases the grasp reflexes returned over a period of weeks but again resolved following definitive cerebrospinal fluid shunting surgery, and remained absent until final follow up at 9 months. We hypothesise that resolving grasp reflexes following high volume CSF removal has both diagnostic and prognostic value in normal pressure hydrocephalus, encouraging larger studies on the relevance of primitive reflexes in NPH.

Comparative durability and costs analysis of ventricular shunts.

PubMed

Agarwal, Nitin; Kashkoush, Ahmed; McDowell, Michael M; Lariviere, William R; Ismail, Naveed; Friedlander, Robert M

2018-05-11

OBJECTIVE Ventricular shunt (VS) durability has been well studied in the pediatric population and in patients with normal pressure hydrocephalus; however, further evaluation in a more heterogeneous adult population is needed. This study aims to evaluate the effect of diagnosis and valve type-fixed versus programmable-on shunt durability and cost for placement of shunts in adult patients. METHODS The authors retrospectively reviewed the medical records of all patients who underwent implantation of a VS for hydrocephalus at their institution over a 3-year period between August 2013 and October 2016 with a minimum postoperative follow-up of 6 months. The primary outcome was shunt revision, which was defined as reoperation for any indication after the initial procedure. Supply costs, shunt durability, and hydrocephalus etiologies were compared between fixed and programmable valves. RESULTS A total of 417 patients underwent shunt placement during the index time frame, consisting of 62 fixed shunts (15%) and 355 programmable shunts (85%). The mean follow-up was 30 ± 12 (SD) months. The shunt revision rate was 22% for programmable pressure valves and 21% for fixed pressure valves (HR 1.1 [95% CI 0.6-1.8]). Shunt complications, such as valve failure, infection, and overdrainage, occurred with similar frequency across valve types. Kaplan-Meier survival curve analysis showed no difference in durability between fixed (mean 39 months) and programmable (mean 40 months) shunts (p = 0.980, log-rank test). The median shunt supply cost per index case and accounting for subsequent revisions was $3438 (interquartile range $2938-$3876) and $1504 (interquartile range $753-$1584) for programmable and fixed shunts, respectively (p < 0.001, Wilcoxon rank-sum test). Of all hydrocephalus etiologies, pseudotumor cerebri (HR 1.9 [95% CI 1.2-3.1]) and previous shunt malfunction (HR 1.8 [95% CI 1.2-2.7]) were found to significantly increase the risk of shunt revision. Within each diagnosis, there were no significant differences in revision rates between shunts with a fixed valve and shunts with a programmable valve. CONCLUSIONS Long-term shunt revision rates are similar for fixed and programmable shunt pressure valves in adult patients. Hydrocephalus etiology may play a significant role in predicting shunt revision, although programmable valves incur higher supply costs regardless of initial diagnosis. Utilization of fixed pressure valves versus programmable pressure valves may reduce supply costs while maintaining similar revision rates. Given the importance of developing cost-effective management protocols, this study highlights the critical need for large-scale prospective observational studies and randomized clinical trials of ventricular shunt valve revisions and additional patient-centered outcomes.

Initial shunt type at the Norwood operation impacts myocardial function in hypoplastic left heart syndrome.

PubMed

Ruotsalainen, Hanna K; Pihkala, Jaana; Salminen, Jukka; Hornberger, Lisa K; Sairanen, Heikki; Ojala, Tiina

2017-08-01

We investigated the impact of initial shunt type, a Blalock-Taussig (BT) shunt versus a right ventricle to pulmonary artery conduit (RV-PA) on myocardial function at different stages of surgical palliation in patients with hypoplastic left heart syndrome (HLHS). A population-based cohort of 63 Finnish children with HLHS (BT n  = 23, RV-PA n  = 40) born between 2003 and 2010 were studied retrospectively by echocardiography prior to Stages 1, 2 and 3 palliation and 0.5-3 years after Stage 3. For comparison of systolic myocardial function, we evaluated the RV fractional area change (FAC), strain, strain rate and mechanical synchrony from the apical 4-chamber view by velocity vector imaging. There were no intergroup differences in demographics during the study period. At baseline, no intergroup differences were detected in RV systolic myocardial function. Before Stage 2, RV FAC was higher ( P  = 0.03) in the RV-PA conduit group. At Stage 3, an increase in all systolic myocardial functional parameters was observed in the BT shunt group. After Stage 3, the BT shunt group had better RV systolic function. In multiple regression analysis, the shunt type and the stage of palliation had an impact on myocardial function. Although patients with HLHS initially palliated with a BT shunt demonstrate lower RV FAC after Stage I, RV FAC improves after Stage 2 with better systolic performance after Stage 3 compared with those initially palliated with an RV-PA conduit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Lower incidence of reoperation with longer shunt survival with adult ventriculoperitoneal shunts placed for hemorrhage-related hydrocephalus.

PubMed

Hoh, Brian L; Lang, Shih-Shan; Ortiz, Michael V; Chi, Yueh-Yun; Lewis, Stephen B; Pincus, David W

2008-07-01

The incidence of reoperation for ventriculoperitoneal shunts (VPS) in adults, although lower than in pediatric patients, is not insignificant. We hypothesize that adult VPS placed for hemorrhage-related hydrocephalus have a lower incidence of reoperation than those placed for other types of hydrocephalus. We retrospectively reviewed all adult (>/= 20 yr) VPS initially placed from February 2001 to August 2006 at the University of Florida. We determined the incidence and time interval to reoperation. Follow-up was conducted by telephone interview and review of medical records. A total of 286 adult VPS were initially placed: 96 (34%) hemorrhage and 190 (66%) nonhemorrhage. A total of 15 (16%) hemorrhage patients underwent 22 shunt reoperations, compared with 50 (27%) nonhemorrhage patients who underwent 82 shunt reoperations (P = 0.0316). A Poisson regression analysis of the number of reoperations, factoring hemorrhage, age, and sex, demonstrated a significantly lower incidence of reoperation in hemorrhage patients (P = 0.0900). A Cox proportional hazards model analysis of time to first reoperation, factoring hemorrhage, age, and sex, demonstrated a significantly longer shunt survival in hemorrhage patients (P = 0.0404). Adult VPS placed for hemorrhage-related hydrocephalus have a significantly lower incidence of reoperation and significantly longer shunt survival. This result may be related to an incidence of transient shunt dependency in patients with hemorrhage-related hydrocephalus. However, the precise mechanism remains unclear.

Segmentation and labeling of the ventricular system in normal pressure hydrocephalus using patch-based tissue classification and multi-atlas labeling

NASA Astrophysics Data System (ADS)

Ellingsen, Lotta M.; Roy, Snehashis; Carass, Aaron; Blitz, Ari M.; Pham, Dzung L.; Prince, Jerry L.

2016-03-01

Normal pressure hydrocephalus (NPH) affects older adults and is thought to be caused by obstruction of the normal flow of cerebrospinal fluid (CSF). NPH typically presents with cognitive impairment, gait dysfunction, and urinary incontinence, and may account for more than five percent of all cases of dementia. Unlike most other causes of dementia, NPH can potentially be treated and the neurological dysfunction reversed by shunt surgery or endoscopic third ventriculostomy (ETV), which drain excess CSF. However, a major diagnostic challenge remains to robustly identify shunt-responsive NPH patients from patients with enlarged ventricles due to other neurodegenerative diseases. Currently, radiologists grade the severity of NPH by detailed examination and measurement of the ventricles based on stacks of 2D magnetic resonance images (MRIs). Here we propose a new method to automatically segment and label different compartments of the ventricles in NPH patients from MRIs. While this task has been achieved in healthy subjects, the ventricles in NPH are both enlarged and deformed, causing current algorithms to fail. Here we combine a patch-based tissue classification method with a registration-based multi-atlas labeling method to generate a novel algorithm that labels the lateral, third, and fourth ventricles in subjects with ventriculomegaly. The method is also applicable to other neurodegenerative diseases such as Alzheimer's disease; a condition considered in the differential diagnosis of NPH. Comparison with state of the art segmentation techniques demonstrate substantial improvements in labeling the enlarged ventricles, indicating that this strategy may be a viable option for the diagnosis and characterization of NPH.

Cine phase-contrast MR imaging in normal pressure hydrocephalus patients: relation to surgical outcome.

PubMed

Egeler-Peerdeman, S M; Barkhof, F; Walchenbach, R; Valk, J

1998-01-01

Phase-contrast cine MR flow imaging through the aqueduct was used to establish the diagnosis of normal pressure hydrocephalus (NPH), and to predict outcome after shunting. From 1990-1994 16 patients, who were participants in the Dutch Normal Pressure Hydrocephalus Study [3], were studied. The patients included in this study met clinical and CT-scan criteria as described in this study, underwent cine phase-contrast MR imaging prior to placement of a CSF shunt, and had a follow-up 12 months after the operation. Claustrophobic patients, patients with a pacemaker or extremely agitated patients were excluded. Normal Flux was calculated in each patients, as the average difference in caudal and rostral flux (Fdiff) +2 times standard deviation (0.97 cc/sec) [2]. The clinical outcome was measured with a modified scale of activities of daily living (ADL) as described by Rankin. Of the 16 patients, 8 could not be evaluated due to restlessness during MR measurements, disabling cerebral vascular accidents or death before the end of the follow-up period. Of the remaining 8 patients, 5 had a normal flux, of which only one improved. Two patients had a Fdiff twice the normal range, which improved in both patients. One patient had no measurable flux, consistent with an aqueduct stenosis; he too improved. Overall, there was a concordance of MR findings with final outcome after shunting in 7 out of 8 patients. This pilot study, therefore, support the need to further evaluate flow with MR imaging techniques to select patients with shunt responsive NPH.

An Automated, Gravity-driven CSF Drainage System Decreases Complications and Lowers Costs

PubMed Central

Lieberson, Robert E; Meyer, William; Trang, Tung

2017-01-01

Background: FlowSafeTM (BeckerSmith Medical, Irvine, CA, USA) is a novel, robotic, external lumbar drainage (ELD) system, which was designed to control cerebrospinal fluid (CSF) drainage, reduce complications, and decrease treatment costs. Methods: Forty-seven consecutive neurosurgical patients requiring ELD were treated using the FlowSafe system. Results: In 39 of 40 patients with traumatic and surgical dural openings, potential CSF leaks were avoided. In seven patients with suspected normal pressure hydrocephalus, post-infectious ventriculomegaly, or pseudotumor cerebrum, we were able to assess the likelihood of improvement with shunting. The system, therefore, produced what we considered to be the “desired result” in 46 of 47 patients (98%). Our one treatment failure (2%) involved a patient with unrecognized hydrocephalus who, following a Chiari repair with a dural patch graft, was drained for six days. A persistent CSF leak eventually required a reoperation. Two patients (4%) described low-pressure headaches during treatment. Both responded to temporarily suspending or reducing the drainage rate. We saw no complications. Required nursing interventions were minimal.  Conclusions: The FlowSafe system was safe and effective. In our experience, there were fewer complications compared to currently available ELD systems. The FlowSafe was well tolerated by our patients. The near elimination of nursing interventions should allow lumbar drainage to be delivered in less costly, non-intensive care unit settings. Larger trials will be needed. PMID:28331772

Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

PubMed

Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

2015-10-01

Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pleocytosis is not fully responsible for low CSF glucose in meningitis.

PubMed

Baud, Maxime O; Vitt, Jeffrey R; Robbins, Nathaniel M; Wabl, Rafael; Wilson, Michael R; Chow, Felicia C; Gelfand, Jeffrey M; Josephson, S Andrew; Miller, Steve

2018-01-01

The mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels. We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis. We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial ( R 2 = 36%, p < 0.001) and repeated CSF sampling ( R 2 = 46%, p < 0.001). Hypoglycorrhachia (<40 mg/dL) was observed in 50.1% of microbial cases, but only 9.6% of aseptic cases, most of which were neurosarcoidosis. Absolute CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used. The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

Management of post-neurosurgical meningitis: narrative review.

PubMed

Hussein, K; Bitterman, R; Shofty, B; Paul, M; Neuberger, A

2017-09-01

Infections complicating neurosurgery pose unacceptable mortality and morbidity. To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria. However, knowledge of the local epidemiology is necessary to treat PNM. The diagnosis of PNM is difficult because, unlike community-acquired meningitis, symptoms are less specific; patients are ill at baseline and many neurosurgical conditions mimic meningitis and cause cerebrospinal fluid (CSF) abnormalities. Pivotal CSF findings for diagnosis of PNM are the CSF glucose, CSF lactate and Gram stain. CSF leucocyte counts are not specific in PNM. Current diagnostic capabilities leave a non-negligible category of patients with microbiologically negative, uncertain diagnosis of PNM. There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement. Some data point to a potential benefit of IV/IT antibiotic treatment, mainly for PNM caused by carbapenem-resistant Gram-negative bacteria. Carbapenem-colistin combination therapy is suggested for PNM caused by carbapenem-resistant Gram-negative bacteria with a carbapenem MIC ≤8 mg/L. Guiding the optimal management of PNM will necessitate collaborative multicentre efforts and unique study designs. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Cross-Species Functionality of Pararetroviral Elements Driving Ribosome Shunting

PubMed Central

Pooggin, Mikhail M.; Fütterer, Johannes; Hohn, Thomas

2008-01-01

Background Cauliflower mosaic virus (CaMV) and Rice tungro bacilliform virus (RTBV) belong to distinct genera of pararetroviruses infecting dicot and monocot plants, respectively. In both viruses, polycistronic translation of pregenomic (pg) RNA is initiated by shunting ribosomes that bypass a large region of the pgRNA leader with several short (s)ORFs and a stable stem-loop structure. The shunt requires translation of a 5′-proximal sORF terminating near the stem. In CaMV, mutations knocking out this sORF nearly abolish shunting and virus viability. Methodology/Principal Findings Here we show that two distant regions of the CaMV leader that form a minimal shunt configuration comprising the sORF, a bottom part of the stem, and a shunt landing sequence can be replaced by heterologous sequences that form a structurally similar configuration in RTBV without any dramatic effect on shunt-mediated translation and CaMV infectivity. The CaMV-RTBV chimeric leader sequence was largely stable over five viral passages in turnip plants: a few alterations that did eventually occur in the virus progenies are indicative of fine tuning of the chimeric sequence during adaptation to a new host. Conclusions/Significance Our findings demonstrate cross-species functionality of pararetroviral cis-elements driving ribosome shunting and evolutionary conservation of the shunt mechanism. We are grateful to Matthias Müller and Sandra Pauli for technical assistance. This work was initiated at Friedrich Miescher Institute (Basel, Switzerland). We thank Prof. Thomas Boller for hosting the group at the Institute of Botany. PMID:18286203

A follow-up study of neonatal interatrial shunt with echocardiography until twelve to fifteen months of age.

PubMed

Ho, Chi-Lin; Jan, Sheng-Ling; Lin, Ming-Chih; Fu, Yun-Ching

2008-12-01

To assess the incidence and natural history of full-term neonates with interatrial shunt (IAS). A follow-up study of 1389 neonates who received screening echocardiography between 2003 and 2006. Babies with IAS at 2 to 4 days of life underwent follow-up echocardiography at 2 to 4 months, 6 to 9 months and 12 to 15 months of age until closure of IAS. The ratio of IAS was 68.3% initially. No significant demographic differences were identified between infants with and without initial IAS. Among 949 neonates with initial IAS, 84.5% infants had a left-to-right interatrial shunt, 13.5% had bidirectional shunt and 2% had predominantly right-to-left shunt. The persistence rate of IAS at 12 to 15 months of age was 3.8% (44/1166). The initial size of IAS ranged from 1.2 to 7.7mm (4.3+/-1.1 mm) detected by color Doppler flow mapping and cases were divided into three groups: small (< or =5 mm), medium (5 to 8 mm) and large group (> or =8 mm). There were 74.6% infants in the small group and 25.4% in the medium group initially. The neonates in the initial small group would always see their IAS close or else they would remain in the small group. Those in the final medium and large size groups always came from the initial medium group. The late closure rate of IAS was 93.9% of infants with initial IAS. The closure curves of initial small and medium sized groups were significantly different, and their late closure rates were 95.1% and 90.4%, respectively. IAS was very common during early neonatal stage, but most cases would close after 1 year. The late closure rate of initial IAS was different if using a cutpoint of 5 mm.

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy.

PubMed

Yilmaz, Aylin; Yiannoutsos, Constantin T; Fuchs, Dietmar; Price, Richard W; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus

2013-05-10

Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.

Ultrasound guided placement of the distal catheter in paediatric ventriculoatrial shunts-an appraisal of efficacy and complications.

PubMed

Clark, David J; Chakraborty, Aabir; Roebuck, Derek J; Thompson, Dominic N P

2016-07-01

Ventriculoatrial (VA) shunts are commonly used as a second-line treatment of hydrocephalus when the peritoneum is an unsuitable site for the distal catheter. Many centres now utilise ultrasound and interventional radiology techniques to aid placement of the distal catheter. The purpose of this study was to conduct a contemporary audit of VA shunting in children using interventional radiology techniques for placement of the distal catheter. A retrospective analysis of all patients who had VA shunts inserted between June 2000 and June 2010 was conducted using a prospectively updated surgical database and case notes review. Ninety-four VA shunts were inserted in 38 patients. Thirty-seven patients had been treated initially with ventriculoperitoneal (VP) shunts. Twenty-two patients required at least 1 shunt revision (58 %). The 6-month, 1- and 2-year shunt survival rates were 53, 43 and 27 %, respectively. Blockage was the commonest reason for shunt failure (68 %). The site of failure was proximal (ventricular catheter +/- valve) in 32 % and distal (atrial catheter) in 21 % of cases. The overall infection rate was 6 % per procedure and 11 % per patient. There were 7 deaths, of which 3 were shunt related. VA shunting provides a viable second-line option for shunt placement in complex hydrocephalus. The causes of shunt failure (blockage, infection and equipment failure) are similar to VP shunting though shunt survival rates are inferior to VP shunts. Ultrasound guided VA shunt placement provides a relatively safe, second-line alternative to the placement of a ventriculoperitoneal shunt when this route is unsuitable.

[Craniotomy without trichotomy: analysis of 640 cases].

PubMed

Dvilevicius, Amylcar E; Machado, Silvio; do Rêgo, José Iram M; Santos, Daniel Souza; Pietrowski, Fábio; Reis, Arnaldo Dias

2004-03-01

The hair shaving in preparation for neurosurgery is frequently used in most of neurosurgical centers to perform craniotomy. We question about its necessity after our retrospective analysis of 640 patients undergoing cranial procedures without previous hair shaving. We had the overall surgical wound infection rate of 1.09%, not higher than tricotomy in the review of the literature. In 7 cases with infection, 3 patients were undergoing to CSF shunts, 3 patients had head injury, and one had brain tumor. The technique for preparing skin and hair for cranial procedures, its advantages and disadvantages are described and discussed.

Endoscopic cystoventriculostomy and ventriculo-cysternostomy using a 2.0 micron fiber guided cw laser in children with hydrocephalus

NASA Astrophysics Data System (ADS)

Ludwig, Hans C.; Kruschat, Thomas; Knobloch, Torsten; Rostasy, Kevin M.; Teichmann, Heinrich O.; Buchfelder, Michael

2005-08-01

Preterm infants have a high incidence of post hemorrhagic or post infectious hydrocephalus often associated with ventricular or arachnoic cysts which carry a high risk of entrapment of cerebrospinal fluid (CSF). In these cases fenestration and opening of windows within the separating membranes are neurosurgical options. In occlusive hydrocephalus caused by aquaeductal stenosis 3rd ventriculostomy is the primary choice of the operative procedures. Although Nd:YAG and diode lasers have already been used in neuroendoscopic procedures, neurosurgeons avoid the use of high energy lasers in proximity to vital structures because of potential side effects. We have used a recently developed diode pumped solid state (DPSS) laser emitting light at a wavelength of 2.0 micron (Revolix TM LISA laser products, Katlenburg, Germany), which can be delivered through silica fibres towards endoscopic targets. From July 2002 until May 2005 22 endoscopic procedures in 20 consecutive patients (age 3 months to 12 years old) were performed. Most children suffered from complex post hemorrhagic and post infectious hydrocephalus, in whom ventriculoperitoneal shunt devices failed to restore a CSF equilibrium due to entrapment of CSF pathways by the cysts. We used two different endoscopes, a 6 mm Neuroendoscope (Braun Aesculap, Melsungen, Germany) and a 4 mm miniature Neuroscope (Storz, Tuttlingen, Germany). The endoscopes were connected to a standard camera and TV monitor, the laser energy was introduced through a 365 micron core diameter bare ended silica fibre (PercuFib, LISA laser products, Katlenburg, Germany) through the endoscope's working channel. The continuous wave laser was operated at power levels from 5 to 15 Watt in continuous and chopped mode. The frequency of the laser in chopped mode was varied between 5 and 20 Hz. All patients tolerated the procedure well. No immediate or long term side effects were noted. In 3 patients with cystic compression of the 4th ventricle, insertion of a shunt device could be avoided. All 3rd ventriculostomies were sufficient for therapy of hydrocephalus, postoperatively MRI scans showed a bright flow void signal. The authors conclude that the use of the new Revolix laser enables safe and effective procedures in neuroendoscopy.

Temporary arterial shunts to maintain limb perfusion after arterial injury: an animal study

NASA Technical Reports Server (NTRS)

Dawson, D. L.; Putnam, A. T.; Light, J. T.; Ihnat, D. M.; Kissinger, D. P.; Rasmussen, T. E.; Bradley, D. V. Jr

1999-01-01

BACKGROUND: Temporary shunt placement can quickly restore perfusion after extremity arterial injury. This study examined the adequacy of limb blood flow with shunt use, non-heparin-bonded shunt patency over prolonged periods, and the safety of this technique. METHODS: Common iliac arteries were divided and 4.0-mm Silastic Sundt shunts placed in 16 anesthetized pigs. Eight (group I) had shunts placed immediately; eight others (group II) were shunted after an hour of limb ischemia and hemorrhagic shock. Physiologic parameters and femoral artery blood flow in both hindlimbs were continuously monitored. Limb lactic acid generation, oxygen utilization, and hematologic and metabolic effects were serially evaluated for 24 hours. RESULTS: Shunts remained patent in 13 of 16 pigs. Shunts thrombosed in two group I animals because of technical errors, but functioned well after thrombectomy and repositioning. Patency could not be maintained in one animal that died from shock. Flow in group I shunted limbs was 57 (+/-11 SD) % of control. For group II animals in shock, shunted limb flow initially averaged 46 +/- 15% of control, but 4 hours after shunt placement, the mean limb blood flow was the same as in group I. Increased oxygen extraction compensated for the lower flow. Lactic acid production was not increased in comparison to control limbs. CONCLUSION: Shunts provided adequate flow in this model of extremity trauma. Correctly placed shunts stayed patent for 24 hours, without anticoagulation, if shunt placement followed resuscitation.

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

PubMed Central

2013-01-01

Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

False-positive cerebrospinal fluid cryptococcus antigen in Libman-Sacks endocarditis.

PubMed

Isseh, Iyad N; Bourgi, Kassem; Nakhle, Asaad; Ali, Mahmoud; Zervos, Marcus J

2016-12-01

Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results. We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay. Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

Congenital intrahepatic portosystemic venous shunt presenting with paraparesis as the initial symptom.

PubMed

Torigoe, Masataka; Maeshima, Keisuke; Takeshita, Yasushi

2013-01-01

An 85-year-old woman was hospitalized with rapidly progressive paraparesis without altered consciousness, although she was not definitively diagnosed. She developed acute drowsiness and disorientation several days later. An intrahepatic portosystemic venous shunt (IPSVS) was observed on enhanced computed tomography, and hyperammonemia suggested leakage of neurotoxins from the shunt as the etiology of the patient's symptoms. Her neurological symptoms and hyperammonemia improved following transcatheter shunt embolization. We diagnosed her with hepatic myelopathy, which is a rare complication of liver cirrhosis and portosystemic venous shunts. Hepatic myelopathy resulting from a congenital IPSVS has not been previously reported. A diagnosis of hepatic myelopathy should be ruled out in diagnostically difficult cases of paraparesis.

Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury.

PubMed

Ost, M; Nylén, K; Csajbok, L; Ohrfelt, A Olsson; Tullberg, M; Wikkelsö, C; Nellgård, P; Rosengren, L; Blennow, K; Nellgård, B

2006-11-14

We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. Patients with severe TBI (n = 39, Glasgow Coma Scale score 2,126 pg/mL on days 2 to 3 discriminated between dead and alive (sensitivity of 100% and a specificity of 81%). A vCSF total tau level of >702 pg/mL on days 2 to 3 discriminated between bad (GOSE 1 to 4) and good (GOSE 5 to 8) outcome (sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury (TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

PubMed Central

Robinson, Shenandoah

2013-01-01

Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is essential because of the declining incidence of IVH and PHH, variations in referral patterns, and neonatal ICU and neurosurgical management. Well-designed multicenter trials will eventually produce evidence to enable neurosurgeons to provide their smallest, most vulnerable patients with the best practices to minimize perioperative complications and permanent shunt dependence, and most importantly, optimize long-term neurodevelopmental outcomes. (http://thejns.org/doi/abs/10.3171/2011.12.PEDS11136) PMID:22380952

Armored brain: A case report and review of the literature.

PubMed

Petraglia, Anthony L; Moravan, Michael J; Jahromi, Babak S

2011-01-01

Calcified chronic subdural hematomas occur infrequently. When the calcifications are extensive and bilateral, the condition is termed "armored brain". We describe a case of "armored brain" incidentally discovered in an adult presenting with abdominal pain and mild headaches, long after initial placement of a ventriculo-peritoneal (VP) shunt. A 38-year-old woman, treated at infancy with a VP shunt, presented with a 2-month history of abdominal pain associated with nausea and chills. She was neurologically intact on exam. An abdominal computed tomography (CT) scan demonstrated a rim-enhancing loculated fluid collection surrounding the patient's distal VP shunt catheter tip. As a part of her initial work-up, she received a head CT to evaluate the proximal VP shunt, which demonstrated large bilateral chronic subdural hematomas with heavily calcified walls. She was eventually taken to the operating room (OR) for replacement of the distal catheter. It was felt that her acute clinical presentation was unrelated to the bilateral, calcified subdural hematomas and thus the decision was made to manage them conservatively. This rare complication of chronic shunting for hydrocephalus is sometimes referred to as armored brain. Surgery for armored brain is infrequently indicated and beneficial in only small subgroup of patients, with management guided by clinical presentation. Our patient fully recovered after shunt revision alone.

Comparing External Ventricular Drains-Related Ventriculitis Surveillance Definitions

PubMed Central

Reyes, Maria; Munigala, Satish; Church, Emily; Kulik, Tobias; Keyrouz, Salah; Zipfel, Gregory; Warren, David K.

2017-01-01

Objective To evaluate the agreement between the current National Healthcare Safety Network (NHSN) definition for ventriculitis and others found in the literature among patients with an external ventricular drain (EVD). Design Retrospective cohort study from January 2009 to December 2014 Setting Neurology and neurosurgery intensive care unit of a large tertiary care center. Patients Patients with an EVD. Patients with an infection prior to EVD placement or a permanent ventricular shunt were excluded. Methods We reviewed the charts of patients with a positive cerebrospinal fluid (CSF) cultures and/or abnormal CSF results while they had an EVD in place and applied various ventriculitis definitions. Results We identified 48 patients with a total of 52 episodes of ventriculitis (41 CSF culture positive episodes and 11 episodes based on abnormal CSF test results) using the NHSN definition. The most common organisms causing ventriculitis were Gram positive commensals (79.2%), however 45% of these had growth of only one colony on one piece of media. About 60% of the ventriculitis episodes by NHSN definition met Honda criteria, about 56% met Gozal criteria and 23% met Citerio’s definition. Honda vs. Gozal had a moderate agreement (Ƙ=0.528, p< 0.05) whereas Honda vs Citerio (Ƙ=0.338, p< 0.05) and Citerio vs Gozal (Ƙ=0.384, p< 0.05) comparisons had only fair agreements. Conclusions Agreement between published VAI definitions in this cohort was moderate to fair. A VAI surveillance definition that better defines contaminants is needed for more homogenous application of surveillance definitions between institutions and better comparison of rates. PMID:28219470

Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus.

PubMed

Kulkarni, Abhaya V; Drake, James M; Mallucci, Conor L; Sgouros, Spyros; Roth, Jonathan; Constantini, Shlomi

2009-08-01

To develop a model to predict the probability of endoscopic third ventriculostomy (ETV) success in the treatment for hydrocephalus on the basis of a child's individual characteristics. We analyzed 618 ETVs performed consecutively on children at 12 international institutions to identify predictors of ETV success at 6 months. A multivariable logistic regression model was developed on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). In the training set, 305/455 ETVs (67.0%) were successful. The regression model (containing patient age, cause of hydrocephalus, and previous cerebrospinal fluid shunt) demonstrated good fit (Hosmer-Lemeshow, P = .78) and discrimination (C statistic = 0.70). In the validation set, 105/163 ETVs (64.4%) were successful and the model maintained good fit (Hosmer-Lemeshow, P = .45), discrimination (C statistic = 0.68), and calibration (calibration slope = 0.88). A simplified ETV Success Score was devised that closely approximates the predicted probability of ETV success. Children most likely to succeed with ETV can now be accurately identified and spared the long-term complications of CSF shunting.

Interventional embolization of congenital intrahepatic shunts in children.

PubMed

Wu, Lin; Zhao, Lu; Lu, Ying; He, Lan; Hu, Xihong

2016-04-01

Congenital intrahepatic shunts in children are rare and precise treatment strategies have not been established. The purpose of this study was to present our experience with transcatheter embolization in a descriptive case series of congenital intrahepatic shunts in children. We retrospectively studied 10 children with symptomatic congenital intrahepatic shunts who were treated with embolization at our institute between January 2008 and December 2014. Seven children had arteriovenous shunts in association with hepatic hemangiomas, two had arterioportal shunts and one had portosystemic shunts. The major presentations were congestive heart failure and severe anemia in the groups with arteriovenous and arterioportal shunts, respectively. Following embolization, two children died in the arteriovenous group, one from progressive liver dysfunction and the other from abdominal compartment syndrome. One child in the arterioportal group required liver transplantation after initial embolization. With mean post-procedure follow-up of 15 months (range 4-54 months), all the remaining children were well, with resolution of the symptoms. Interventional embolization provides an alternative to surgical ligation or hepatic resection in children with clinically significant intrahepatic shunts. For lesions with complex morphology, embolization may be inadequate and liver transplantation might be the only therapeutic option.

Optimum Design of Anti-Siphon Device used to Prevent Cerebrospinal Fluid from Overdraining

NASA Astrophysics Data System (ADS)

Jang, Jong Yun; Lee, Chong Sun; Suh, Chang Min

The present study investigated design parameters of an anti-siphon device used with shunt valves to treat patients with hydrocephalus. Structural analyses were performed to understand roles of design variables and optimize performance of the diaphragm-type anti-siphon device (hereafter referred to as the ASD). Experiments were performed on the lab-made product and showed good agreements with the numerical simulations. Using the simulations, we were able to design a more physiological ASD which gave equal opening pressures in both supine and upright postures. Tissue encapsulization phenomenon was also simulated and the results indicated underdrainage of CSF in the upright position of the patient.

An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy

PubMed Central

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W.; Palmer, Sarah

2014-01-01

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system. PMID:24338353

An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy.

PubMed

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W; Palmer, Sarah

2014-05-15

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

PubMed

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

2009-04-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

PubMed Central

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

2009-01-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD. PMID:19390619

Poor cognitive outcome in shunt-responsive idiopathic normal pressure hydrocephalus.

PubMed

Koivisto, Anne M; Alafuzoff, Irina; Savolainen, Sakari; Sutela, Anna; Rummukainen, Jaana; Kurki, Mitja; Jääskeläinen, Juha E; Soininen, Hilkka; Rinne, Jaakko; Leinonen, Ville

2013-01-01

Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce. To elucidate the long-term cognitive condition of shunt-responsive iNPH patients. The follow-up data (Kuopio University Hospital NPH Registry) of 146 patients diagnosed with iNPH by clinical and radiological examination, 24-hour intraventricular pressure monitoring, frontal cortical biopsy, and response to the shunt were analyzed for signs of dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Median follow-up was 4.8 years. At the end of follow-up, 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had clinical dementia. The most common clinical diagnoses were Alzheimer disease and vascular dementia. In multivariate analysis of the 146 iNPH patients, memory deficit as a first symptom before shunt (odds ratio [OR] 18.3; 95% confidence interval [CI] 1.9-175), male sex (OR 3.29; 95% CI 1.11-9.73), age (OR 1.17 year; 95% CI 1.07-1.28), and follow-up time (OR 1.20 year; 95% CI 1.02-1.40) predicted dementia. Interestingly, 8 (5%) iNPH patients had dementia without any signs of other neurodegenerative diseases in clinical, neuroradiological, or brain biopsy evaluation. These patients initially presented a full triad of symptoms, with gait disturbance being the most frequent initial symptom followed by deterioration in cognition. The novel findings were (a) a significant risk of dementia in iNPH initially responsive to cerebrospinal fluid shunt, (b) cognitive impairment most commonly due to iNPH-related dementia followed by concurrent degenerative brain disease, and (c) a subgroup with dementia related to iNPH without comorbidities.

Armored brain: A case report and review of the literature

PubMed Central

Petraglia, Anthony L.; Moravan, Michael J.; Jahromi, Babak S.

2011-01-01

Background: Calcified chronic subdural hematomas occur infrequently. When the calcifications are extensive and bilateral, the condition is termed “armored brain”. We describe a case of “armored brain” incidentally discovered in an adult presenting with abdominal pain and mild headaches, long after initial placement of a ventriculo-peritoneal (VP) shunt. Case Description: A 38-year-old woman, treated at infancy with a VP shunt, presented with a 2-month history of abdominal pain associated with nausea and chills. She was neurologically intact on exam. An abdominal computed tomography (CT) scan demonstrated a rim-enhancing loculated fluid collection surrounding the patient's distal VP shunt catheter tip. As a part of her initial work-up, she received a head CT to evaluate the proximal VP shunt, which demonstrated large bilateral chronic subdural hematomas with heavily calcified walls. She was eventually taken to the operating room (OR) for replacement of the distal catheter. It was felt that her acute clinical presentation was unrelated to the bilateral, calcified subdural hematomas and thus the decision was made to manage them conservatively. Conclusions: This rare complication of chronic shunting for hydrocephalus is sometimes referred to as armored brain. Surgery for armored brain is infrequently indicated and beneficial in only small subgroup of patients, with management guided by clinical presentation. Our patient fully recovered after shunt revision alone. PMID:21918735

[A case of non-traumatic tension pneumocephalus 12 years after initial ventriculo-peritoneal shunt].

PubMed

Idei, Masaru; Yamane, Kanji; Okita, Shinji; Kumano, Kiyoshi; Nakae, Ryuta; Nishizawa, Shigeru

2009-10-01

The authors presented a patient with non-traumatic tension pneumocephalus 12 years after initial ventriculo-peritoneal shunt. A 60-year-old man had a past history of subarachnoid hemorrhage. At ÿtime, he underwent clipping surgery and emplacement of a ventriculoperitoneal shunt with a low pressure valve, and was discharged from hospital in a bedridden condition. After 12 years, he was transferred to our hospital because of dysarthria and right hemiparesis. On admission, he had multiple dimples of the scalp in the left frontal area where craniotomy had been carried out 12 years before. Head CT scan revealed air located mainly in bilateral subdural space and collapsed ventricles. We suspected that he had a tension pneumocephalus through a scalp-subdural fistula induced by long-term low intracranial pressure. Operation for closure of the fistula was intended. During the operation a subdural abscess was found so, artificial bone and the shunt system was removed. We were able to detect the fistula from the defect of the scalp to the subdural space and closed it by repairing a scalp defect, using dural plasty. Postoperative clinical course was uneventful and the patient was discharged. About 6 month after the operation, cranioplasty and lumbo-peritoneal shunt was performed. We must recognize that appropriate management of intracranial pressure after installation of a ventriculo-peritoneal shunt is necessary for prevention of tension pneumocephalus.

Comparing External Ventricular Drains-Related Ventriculitis Surveillance Definitions.

PubMed

Reyes, Maria M; Munigala, Satish; Church, Emily L; Kulik, Tobias B; Keyrouz, Salah G; Zipfel, Gregory J; Warren, David K

2017-05-01

OBJECTIVE To evaluate the agreement between the current National Healthcare Safety Network (NHSN) definition for ventriculitis and others found in the literature among patients with an external ventricular drain (EVD) DESIGN Retrospective cohort study from January 2009 to December 2014 SETTING Neurology and neurosurgery intensive care unit of a large tertiary-care center PATIENTS Patients with an EVD were included. Patients with an infection prior to EVD placement or a permanent ventricular shunt were excluded. METHODS We reviewed the charts of patients with positive cerebrospinal fluid (CSF) cultures and/or abnormal CSF results while they had an EVD in place and applied various ventriculitis definitions. RESULTS We identified 48 patients with a total of 52 cases of ventriculitis (41 CSF culture-positive cases and 11 cases based on abnormal CSF test results) using the NHSN definition. The most common organisms causing ventriculitis were gram-positive commensals (79.2%); however, 45% showed growth of only 1 colony on 1 piece of media. Approximately 60% of the ventriculitis cases by the NHSN definition met the Honda criteria, approximately 56% met the Gozal criteria, and 23% met Citerio's definition. Cases defined using Honda versus Gozal definitions had a moderate agreement (κ=0.528; P<.05) whereas comparisons of Honda versus Citerio definitions (κ=0.338; P<.05) and Citerio versus Gozal definitions (κ=0.384; P<.05) had only fair agreements. CONCLUSIONS The agreement between published ventriculostomy-associated infection (VAI) definitions in this cohort was moderate to fair. A VAI surveillance definition that better defines contaminants is needed for more homogenous application of surveillance definitions between institutions and better comparison of rates. Infect Control Hosp Epidemiol 2017;38:574-579.

Chiari I malformation with underlying pseudotumor cerebri: Poor symptom relief following posterior decompression surgery.

PubMed

Alnemari, Ahmed; Mansour, Tarek R; Gregory, Stephanie; Miller, William K; Buehler, Mark; Gaudin, Daniel

2017-01-01


 Pseudotumor cerebri (PTC) patients exhibit clear clinical signs and symptoms of higher intracranial pressure (ICP) without ventricular enlargement or mass lesions. The clinical picture of patients with PTC can sometimes be similar to that of Chiari Malformation type I (CMI). There is some evidence that Chiari I malformation and PTC may coexist, which raises the question of whether PTC is an idiopathic disease or a complication of posterior decompression surgery-treatment of choice for Chiari I malformation. A retrospective review of electronic medical records of patients diagnosed with PTC at the University of Toledo Medical Center (UTMC) was performed. The objective was to determine whether PTC patients had a concurrent diagnosis of Chiari I malformation and whether the diagnosis of PTC occurred before or after posterior decompression surgery. Out of the 8 eligible patient medical records reviewed, 5 patients diagnosed with PTC had undergone posterior decompression surgery for Chiari I malformation at anywhere from several days to three years prior to being diagnosed with PTC. The diagnosis of PTC was based on temporary symptomatic relief following lumbar puncture which also showed elevated CSF opening pressures. Finally, a VP shunt was placed in each of the 5 patients to relieve the elevated intracranial pressure which resulted in the complete resolution of the patients' symptoms. Our study focuses on patients who were diagnosed with and treated for CMI then reported back to the clinic within several days to three years complaining of symptoms of headache. Upon re-presenting to the clinic, a CSF flow study was performed which showed normal flow of CSF. Then, these patients underwent a lumbar puncture which demonstrated an elevated opening pressure (and ICP) and a temporary relief of the headache with lumbar drainage. A VP shunt was placed for each patient to treat for PTC, and the patients' headaches were relieved. This study suggests that the presence of Chiari I malformation in a patient conceals the symptoms of PTC which may become apparent following posterior decompression surgery. Other possibilities could be that the patients are misdiagnosed for Chiari I malformation when they are in fact suffering from PTC, or that PTC is a complication of surgery. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Slit ventricle syndrome and early-onset secondary craniosynostosis in an infant

PubMed Central

Ryoo, Hyun Gee; Kim, Seung-Ki; Cheon, Jung-Eun; Lee, Ji Yeoun; Wang, Kyu-Chang; Phi, Ji Hoon

2014-01-01

Patient: Female, 14 months Final Diagnosis: Slit ventricle syndrome Symptoms: Hydrocephalus • lethargy and seizure • vomiting Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Challenging differential diagnosis Background: Shunt surgery is a common solution for hydrocephalus in infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset complications after shunt placement; these 2 conditions occasionally occur together. Case Report: We report a case of early-onset secondary craniosynostosis with slit ventricle syndrome after shunt surgery in an infant, which led to a catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her head circumference (HC) gradually decreased to approximately the 5th percentile for her age group after shunt surgery. Seven months later, she developed increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt malfunction. Her symptoms were temporarily relieved, but she repeatedly visited the emergency room (ER) for the same symptoms and finally collapsed, with an abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence of sagittal synostosis at 7 months after initial shunt surgery. After reviewing all clinical data, slit ventricle syndrome combined with secondary craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt revision was performed, and the increased ICP signs subsided in the following days. Conclusions: Clinical suspicion and long-term HC monitoring are important in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after shunt surgery, even in infants and young children. PMID:24944727

Paradoxical immune reconstitution inflammatory syndrome associated with previous Cryptococcus neoformans infection in an HIV-positive patient requiring neurosurgical intervention.

PubMed

Biagetti, Carlo; Nicola, Monica; Borderi, Marco; Pavoni, Michele; Tampellini, Livia; Verucchi, Gabriella; Chiodo, Francesco

2009-04-01

Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is associated with an exaggerated inflammatory response against an opportunistic infection during highly active antiretroviral therapy. The only review on IRIS associated with Criptococcus neoformans reported 21 episodes including lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and cryptococcomas. To our knowledge this is the first report of IRIS associated with previous meningeal criptococcal infection which required neurosurgical intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst formed by exclusion of the temporal horn of the right lateral ventricle. We demonstrate that this procedure is possible without complications such as cryptococcal dissemination into the peritoneum.

[Idiopathic intracranial hypertension: a caesarean with epidural anaesthesia after bringing the cerebrospinal fluid pressure back to normal].

PubMed

Pérez Rodríguez, M; de Carlos Errea, J; Dorronsoro Auzmendi, M; Batllori Gastón, M

2013-12-01

Idiopathic intracranial hypertension is diagnosed by exclusion. Because of its uncertain physiopathology and infrequent occurrence, its anaesthetic management is not well defined. The patient in this case is a pregnant woman with this disease with no lumbar-peritoneal shunt who was referred for non-urgent caesarean section, consisting of CSF drainage and pressure normalisation before the administration of epidural anaesthesia. We believe this technique can de effective to achieve adequate blockage and increased patient comfort, as well as improving postoperative recovery. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

CSF-1R Inhibitor Development: Current Clinical Status.

PubMed

Peyraud, Florent; Cousin, Sophie; Italiano, Antoine

2017-09-05

Colony-stimulating factor 1 receptor (CSF-1R) and its ligands, CSF-1 and interleukin 34 (IL-34), regulate the function and survival of tumor-associated macrophages, which are involved in tumorigenesis and in the suppression of antitumor immunity. Moreover, the CSF-1R/CSF-1 axis has been implicated in the pathogenesis of pigmented villonodular synovitis (PVNS), a benign tumor of the synovium. As advanced or metastatic malignant solid tumors and relapsed/refractory PVNS remain unresolved therapeutic problems, new approaches are needed to improve the outcome of patients with these conditions. In solid tumors, targeting CSF-1R via either small molecules or antibodies has shown interesting results in vitro but limited antitumor activity in vivo. Concerning PVNS, clinical trials assessing CSF-1R inhibitors have revealed promising initial outcomes. Blocking CSF-1/CSF-1R signaling represents a promising immunotherapy approach and several new potential combination therapies for future clinical testing.

Frequency of Alzheimer's Disease Pathology at Autopsy in Patients with Clinical Normal Pressure Hydrocephalus

PubMed Central

Cabral, Danielle; Beach, Thomas G; Vedders, Linda; Sue, Lucia I; Jacobson, Sandra; Myers, Kent; Sabbagh, Marwan N

2011-01-01

Background Normal pressure hydrocephalus (NPH) is considered potentially treatable with the placement of a cerebrospinal fluid (CSF) shunt. Yet, the procedure has had variable success, particularly with respect to improving the cognitive impairment in NPH. The presence of neurologic co-morbidities, particularly Alzheimer's Disease (AD), may contribute to shunt responsiveness. Uncovering the extent to which AD and NPH co-occur has implications for diagnosis and treatment of NPH. Autopsy studies of patients with NPH during life would elucidate the frequency of such co-morbidities. Methods We conducted a search of the Sun Health Research Institute Brain Donation Program database between 1/1/1997 and 4/1/09 to identify all cases with neuropathologic evidence of dementia as well as those cases of clinically diagnosed NPH. We reviewed the medical records and brain findings of each NPH case. Results Of the 761 cases autopsied over the study interval, 563 cases were found to have neuropathological evidence meeting criteria for a dementing illness. AD was found exclusively in 313/563 (56%) cases with 94/563 cases having a secondary diagnosis of dementia. We identified 9/761 cases with a clinical diagnosis of NPH, all nine cases were among the 563 cases with neuropathology of dementing illness at autopsy, representing 1.6% (9/563). Upon review of brain autopsy reports, 8/9 (89%) cases were found to have AD and 1/9 (11%) had progressive supranuclear palsy. Review of the medical records of the nine NPH cases revealed the following clinical co-morbidities: 5/9 with AD; 1/9 with Parkinson's Disease (PD); 1/9 with Mild Cognitive Impairment (MCI); 1/9 with seizure disorder. Conclusions Given the findings of our study, we support the AD-NPH theory and posit that AD is a common pathological co-morbidity in the setting of NPH and may preclude cognitive improvement post-shunt placement. This may have influence on selection of cases for shunting in the future. PMID:21723206

New concept of the pathogenesis and therapeutic orientation of acquired communicating hydrocephalus.

PubMed

Xu, Hao

2016-09-01

Hydrocephalus is a common medical condition characterized by abnormalities in the secretion, circulation and absorption of cerebrospinal fluid (CSF), resulting in ventricle dilatation. For the communicating hydrocephalus, without etiological treatment, its pathogenesis has been considered as a research emphasis. Many factors can damage the CSF system and trigger communicating hydrocephalus, including tumor surgery and hydrocephalus neurological diseases, such as brain trauma, infection, ICH and SAH. But according to our clinical experience, a big proportion of patients do not develop hydrocephalus. That is because the absorbing ability of CSF can compensate within a certain range. If the damage exceeds that range, hydrocephalus will occur. Once it occurs, it is not likely to be reversed, so a shunt surgery is always needed. Therefore, we believe that our orientation could transform the treatment of patient who has already showed hydrocephalus symptoms to the prevention of the occurrence in the patient with high risk of hydrocephalus. Based on the hypothesis above, we first divide the process of hydrocephalus into three stages and we believe that hydrocephalus are possible be reversed or halted in stage 1 and 2. The new concept of the pathogenesis in hydrocephalus will enrich our understanding and provide new insights to the therapeutic orientation. In conclusion, the future research direction should be the prevention of hydrocephalus, which should take a long period from the immediate occurrence of brain injury to several months or even years after the injury.

Natural history of idiopathic normal-pressure hydrocephalus.

PubMed

Toma, Ahmed K; Stapleton, Simon; Papadopoulos, Marios C; Kitchen, Neil D; Watkins, Laurence D

2011-10-01

Natural history of idiopathic normal-pressure hydrocephalus (INPH) is not clear. We performed a literature search for studies that looked into the outcome of unshunted INPH patients trying to answer the following questions: Do all INPH patients deteriorate without shunt? If yes, at what rate? Do some NPH patients improve without shunt? If yes, to what extent? Six studies objectively described the outcome of 102 INPH patients. Result shows that without surgery, most INPH patients had measurable deterioration as early as 3 months following initial assessment. A small number of patients might improve without shunt, however the extent of improvement is not clear. The homogeneity of the findings of the cohort studies provided high evidence supporting the rule of shunt surgery in INPH patients.

Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.

PubMed

El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun

2018-01-17

Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.

Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial

PubMed Central

Scriven, James E.; Rhein, Joshua; Hullsiek, Katherine Huppler; von Hohenberg, Maximilian; Linder, Grace; Rolfes, Melissa A.; Williams, Darlisha A.; Taseera, Kabanda; Meya, David B.; Meintjes, Graeme; Boulware, David R.

2015-01-01

Introduction. Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome. Methods. Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis. Results. More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation. Conclusions. Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated. PMID:25651842

Endoscopic third ventriculostomy

PubMed Central

Yadav, Yad Ram; Parihar, Vijay; Pande, Sonjjay; Namdev, Hemant; Agarwal, Moneet

2012-01-01

Endoscopic third ventriculostomy (ETV) is considered as a treatment of choice for obstructive hydrocephalus. It is indicated in hydrocephalus secondary to congenital aqueductal stenosis, posterior third ventricle tumor, cerebellar infarct, Dandy-Walker malformation, vein of Galen aneurism, syringomyelia with or without Chiari malformation type I, intraventricular hematoma, post infective, normal pressure hydrocephalus, myelomeningocele, multiloculated hydrocephalus, encephalocele, posterior fossa tumor and craniosynostosis. It is also indicated in block shunt or slit ventricle syndrome. Proper Pre-operative imaging for detailed assessment of the posterior communicating arteries distance from mid line, presence or absence of Liliequist membrane or other membranes, located in the prepontine cistern is useful. Measurement of lumbar elastance and resistance can predict patency of cranial subarachnoid space and complex hydrocephalus, which decides an ultimate outcome. Water jet dissection is an effective technique of ETV in thick floor. Ultrasonic contact probe can be useful in selected patients. Intra-operative ventriculo-stomography could help in confirming the adequacy of endoscopic procedure, thereby facilitating the need for shunt. Intraoperative observations of the patent aqueduct and prepontine cistern scarring are predictors of the risk of ETV failure. Such patients may be considered for shunt surgery. Magnetic resonance ventriculography and cine phase contrast magnetic resonance imaging are effective in assessing subarachnoid space and stoma patency after ETV. Proper case selection, post-operative care including monitoring of ICP and need for external ventricular drain, repeated lumbar puncture and CSF drainage, Ommaya reservoir in selected patients could help to increase success rate and reduce complications. Most of the complications develop in an early post-operative, but fatal complications can develop late which indicate an importance of long term follow up. PMID:22865970

Parent ratings of executive functioning in children with shunted hydrocephalus.

PubMed

Lacy, Maureen; Baldassarre, Megan; Nader, Todd; Frim, David

2012-01-01

The present study examined the executive functioning of a group of children with a history of communicating hydrocephalus and how their level of functioning was correlated with parent ratings of executive functioning. The study examined the executive functioning of 39 shunted children with a history of hydrocephalus and 20 healthy peers. Additionally, parents of both groups of children completed the Behavior Rating Inventory of Executive Function (BRIEF) to assess the parents' perceptions of their children's executive functioning. Finally, the study investigated the relationship between the shunted hydrocephalus children's executive functioning and the parent ratings of their executive functioning. Overall, the children with a history of shunted hydrocephalus displayed more executive dysfunction than their healthy peers. These children were rated by their parents as having more executive dysfunction than their healthy peers and displaying working memory, initiation, mental flexibility and self-monitoring difficulties, which appear to increase with age among the shunted hydrocephalus group. While parent ratings as measured by the BRIEF indices did not correlate with all executive tasks within the shunted hydrocephalus group, the cognitive tests assessing mental flexibility may be sensitive to the problems noted by parents at home. The children with a history of shunted hydrocephalus displayed executive functioning deficits on formal examination. The parents of children with a history of shunted hydrocephalus report ongoing executive difficulties which may increase with age. Copyright © 2012 S. Karger AG, Basel.

Use of the proGAV shunt valve in normal-pressure hydrocephalus.

PubMed

Toma, Ahmed K; Tarnaris, Andrew; Kitchen, Neil D; Watkins, Laurence D

2011-06-01

Overdrainage is a common complication associated with shunt insertion in normal-pressure hydrocephalus (NPH) patients. Using adjustable valves with antigravity devices has been shown to reduce its incidence. The optimal starting setting of an adjustable shunt valve in NPH is debatable. To audit our single-center practice of setting adjustable valves. We performed a retrospective review of clinical records of all NPH patients treated in our unit between 2006 and 2009 by the insertion of shunts with a proGAV valve, recording demographic and clinical data, shunt complications, and revision rates. Radiological reports of postoperative follow-up computed tomography scans of the brain were reviewed for detected subdural hematomas. A proGAV adjustable valve was inserted in 50 probable NPH patients between July 2006 and November 2009. Mean ± SD age was 76 ± 7 years. Mean follow-up was 15 months. The initial shunt setting was 6 ± 3 cm H2O, and the final setting was 4.9 ± 1.9 cm H2O. Nineteen patients required 24 readjustment procedures (readjustment rate, 38%; readjustment number, 0.48 times per patient). One patient (2%) developed delayed bilateral subdural hematoma after readjustment of his shunt valve setting as an outpatient. Starting with a low opening pressure setting on a proGAV adjustable shunt valve does not increase the chances of overdrainage complications and reduces the need for repeated readjustments.

Combined intracranial pressure monitoring and cerebrospinal fluid infusion study to guide management of slit ventricle syndrome.

PubMed

Hart, Michael Gavin; Czosnyka, Marek; Czosnyka, Zofia Helena; Fernandes, Helen Marie

2013-01-01

Slit ventricle syndrome remains a complex entity presenting a considerable challenge to treat successfully. This study aims to demonstrate the application of dual intracranial pressure (ICP) and infusion studies together with the novel shunt occlusion test in both a diagnostic and therapeutic role. An 8-year-old child had aqueduct stenosis treated with a ventriculoperitoneal shunt (medium-pressure valve). The presentation was of headaches with papilloedema. Imaging with both computed tomography and magnetic resonance imaging revealed slit ventricles. Initially a shunt exploration revealed distal obstruction that was treated together with insertion of a paediatric strata II regular valve; however, the child continued to deteriorate. Overnight ICP monitoring revealed dramatically raised ICP with poor compensatory reserve. Intra-operative infusion study revealed a shunt that was patent distally but with proximal obstruction. A subtemporal decompression ipsilateral to the shunt was performed together with adjustment of the paediatric strata II regular valve to 2.5 in order to prevent overdrainage. This led to normalisation of ICP, resolution of papilloedema and symptomatic improvement. We demonstrate how combined ICP monitoring and shunt infusion studies can be used to help guide management. Unilateral subtemporal decompressions and preventing shunt overdrainage can result in normalisation of ICP and cerebrospinal fluid dynamics.

Failed Ventriculoperitoneal Shunt: Is Retrograde Ventriculosinus Shunt a Reliable Option?

PubMed

Oliveira, Matheus Fernandes de; Teixeira, Manoel Jacobsen; Reis, Rodolfo Casimiro; Petitto, Carlo Emanuel; Gomes Pinto, Fernando Campos

2016-08-01

Currently, the treatment of hydrocephalus is mainly carried out through a ventriculoperitoneal shunt (VPS) insertion. However, in some cases, there may be surgical revisions and requirement of an alternative distal site for shunting. There are several described distal sites, and secondary options after VPS include ventriculopleural and ventriculoatrial shunt, which have technical difficulties and harmful complications. In this preliminary report we describe our initial experience with retrograde ventriculosinus shunt (RVSS) after failed VPS. In 3 consecutive cases we applied RVSS to treat hydrocephalus in shunt-dependent patients who had previously undergone VPS revision and in which peritoneal space was full of adhesions and fibrosis. RVSS was performed as described by Shafei et al., with some modifications to each case. All 3 patients kept the same clinical profile after RVSS, with no perioperative or postoperative complications. However, revision surgery was performed in the first operative day in 1 out of 3 patients, in which the catheter was not positioned in the superior sagittal sinus. We propose that in cases where VPS is not feasible, RVSS may be a safe and applicable second option. Nevertheless, the long-term follow-up of patients and further learning curve must bring stronger evidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical strategy according to the anatomical types of congenital portosystemic shunts in children.

PubMed

Matsuura, Toshiharu; Takahashi, Yoshiaki; Yanagi, Yusuke; Yoshimaru, Koichiro; Yamamura, Kenichiro; Morihana, Eiji; Nagata, Hazumu; Uike, Kiyoshi; Takada, Hidetoshi; Taguchi, Tomoaki

2016-12-01

Congenital portosystemic shunts (CPSS) with intrahepatic portal vein (IHPV) hypoplasia or absence cause encephalopathy or pulmonary hypertension (PH). Acute shunt closure may result in postoperative portal hypertension. The aim of this study was to propose a surgical strategy according to the anatomical types of CPSS and IHPV. Twenty-three CPSS patients were diagnosed from1990 to 2015. All patients were evaluated by computed tomography, angiography, and PV pressure monitoring under a shunt occlusion test. CPSS were categorized into 5 types according to the anatomical shunt location. The median age at diagnosis was 34months. Three of 23 total patients, who had an extrahepatic portosystemic shunt with a hypoplastic IHPV, died before treatment initiation because of severe PH. Fourteen cases received surgical or interventional treatment at the median age of 5years. A total of 6 cases received surgical therapy, including liver transplants for 2 absent IHPV cases. The remaining 8 cases received interventional coiling. All shunt ligations were successfully accomplished in 1-stage ligation without any complications. After the treatment, the hypoplastic IHPV gradually enlarged with an efficient portal inflow. A precise pretreatment anatomical evaluation of CPSS and IHPV types is mandatory for the selection of surgical treatment. Diagnostic study - level II and treatment study - level III. Copyright © 2016 Elsevier Inc. All rights reserved.

Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom.

PubMed

Tong, Man-Li; Liu, Li-Li; Zeng, Yan-Li; Zhang, Hui-Lin; Liu, Gui-Li; Zheng, Wei-Hong; Dong, Jie; Wu, Jing-Yi; Su, Yuan-Hui; Lin, Li-Rong; Yang, Tian-Ci

2013-04-01

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS. Copyright © 2013 Elsevier Inc. All rights reserved.

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

PubMed

Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

2018-06-19

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Postprandial hyperinsulinaemic hypoglycaemia secondary to a congenital portosystemic shunt.

PubMed

Senniappan, Senthil; Pitt, Katherine; Shah, Pratik; Arya, Ved; Jaiswal, Sanjay; Haddad, Munther; Hind, Jonathan; Dhawan, Anil; Davenport, Mark; Hussain, Khalid

2015-01-01

Portosystemic shunts (PSS) are abnormal vascular connections between the portal vein or its tributaries and the systemic vein that allow mesenteric blood to reach the systemic circulation without first passing through the liver. PSS can be associated with various syndromes and can lead to serious complications. We report a rare case of a child with PSS and recurrent hypoglycaemia. A 20-month-old girl with Down's syndrome presented with recurrent hypoglycaemic episodes. She had multiple anomalies including a ventricular septal defect, oesophageal atresia and tracheo-esophageal fistula, gastro-oesophageal reflux, and conjugated hyperbilirubinaemia. The initial investigations suggested hyperinsulinaemic hypoglycaemia (HH). She did not respond to diazoxide. An oral glucose tolerance test suggested postprandial HH. Further vascular imaging showed a side-to-side portocaval shunt (Abernethy malformation) with relative hypoperfusion of the liver. Hypoglycaemia resolved following surgical closure of the portocaval shunt. PSS can rarely be associated with HH, possibly due to lack of insulin degradation in the liver. Surgical closure of the shunt resolves the hypoglycaemia. © 2015 S. Karger AG, Basel.

Single pulse analysis of intracranial pressure for a hydrocephalus implant.

PubMed

Elixmann, I M; Hansinger, J; Goffin, C; Antes, S; Radermacher, K; Leonhardt, S

2012-01-01

The intracranial pressure (ICP) waveform contains important diagnostic information. Changes in ICP are associated with changes of the pulse waveform. This change has explicitly been observed in 13 infusion tests by analyzing 100 Hz ICP data. An algorithm is proposed which automatically extracts the pulse waves and categorizes them into predefined patterns. A developed algorithm determined 88 %±8 % (mean ±SD) of all classified pulse waves correctly on predefined patterns. This algorithm has low computational cost and is independent of a pressure drift in the sensor by using only the relationship between special waveform characteristics. Hence, it could be implemented on a microcontroller of a future electromechanic hydrocephalus shunt system to control the drainage of cerebrospinal fluid (CSF).

The CHESS score: a simple tool for early prediction of shunt dependency after aneurysmal subarachnoid hemorrhage.

PubMed

Jabbarli, R; Bohrer, A-M; Pierscianek, D; Müller, D; Wrede, K H; Dammann, P; El Hindy, N; Özkan, N; Sure, U; Müller, O

2016-05-01

Acute hydrocephalus is an early and common complication of aneurysmal subarachnoid hemorrhage (SAH). However, considerably fewer patients develop chronic hydrocephalus requiring shunt placement. Our aim was to develop a risk score for early identification of patients with shunt dependency after SAH. Two hundred and forty-two SAH individuals who were treated in our institution between January 2008 and December 2013 and survived the initial impact were retrospectively analyzed. Clinical parameters within 72 h after the ictus were correlated with shunt dependency. Independent predictors were summarized into a new risk score which was validated in a subsequent SAH cohort treated between January and December 2014. Seventy-five patients (31%) underwent shunt placement. Of 23 evaluated variables, only the following five showed independent associations with shunt dependency and were subsequently used to establish the Chronic Hydrocephalus Ensuing from SAH Score (CHESS, 0-8 points): Hunt and Hess grade ≥IV (1 point), location of the ruptured aneurysm in the posterior circulation (1 point), acute hydrocephalus (4 points), the presence of intraventricular hemorrhage (1 point) and early cerebral infarction on follow-up computed tomography scan (1 point). The CHESS showed strong correlation with shunt dependency (P = 0.0007) and could be successfully validated in both internal SAH cohorts tested. Patients scoring ≥6 CHESS points had significantly higher risk of shunt dependency (P < 0.0001) than other patients. The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies. © 2016 EAN.

Liquid breathing - Prevention of pulmonary arterial-venous shunting during acceleration.

NASA Technical Reports Server (NTRS)

Sass, D. J.; Ritman, E. L.; Caskey, P. E.; Banchero, N.; Wood, E. H.

1972-01-01

Dependent pulmonary atelectasis, arterial-venous shunting, and downward displacement of the heart caused by the gravitational-inertial force environment were prevented in dogs breathing oxygenated liquid fluorocarbon in a whole-body water-immersion respirator. Partial closure of the major airways during part of the expiratory phase of liquid respiration was a significant problem initially but was minimized in subsequent studies.

The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.

PubMed

de Leon, Mony J; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; Saint-Louis, Les; Kim, Hee-Jin; Fortea, Juan; Fossati, Silvia; Laska, Eugene; Siegel, Carole; Butler, Tracy; Li, Yi; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj

2018-01-01

Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.

CSF1R mutations in hereditary diffuse leukoencephalopathy with spheroids are loss of function

NASA Astrophysics Data System (ADS)

Pridans, Clare; Sauter, Kristin A.; Baer, Kristin; Kissel, Holger; Hume, David A.

2013-10-01

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) in humans is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the CNS white matter. Symptoms are variable and can include personality and behavioural changes. Patients with this disease have mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. We investigated the effects of these mutations on Csf1r signalling using a factor dependent cell line. Corresponding mutant forms of murine Csf1r were expressed on the cell surface at normal levels, and bound CSF1, but were not able to sustain cell proliferation. Since Csf1r signaling requires receptor dimerization initiated by CSF1 binding, the data suggest a mechanism for phenotypic dominance of the mutant allele in HDLS.

Treatment options for Dandy-Walker malformation.

PubMed

Mohanty, Aaron; Biswas, Arundhati; Satish, Satyanarayana; Praharaj, Shanti Shankar; Sastry, Kolluri V R

2006-11-01

The aim of this study was to assess the efficacy of various treatment options available for children with Dandy-Walker malformation (DWM) and to evaluate the role of endoscopic procedures in the treatment of this disorder. The authors conducted a retrospective review of 72 children who underwent surgical treatment for DWM during a 16-year period. All patients underwent computed tomography scanning, and 26 underwent magnetic resonance (MR) imaging. The initial surgical treatment included ventriculoperitoneal (VP) shunt placement in 21 patients, cystoperitoneal (CP) shunt placement in 24, and combined VP and CP shunt insertion in three. Twenty-one patients underwent endoscopic procedures (endoscopic third ventriculostomy [ETV] alone in 16 patients, ETV with aqueductal stent placement in three, and ETV with fenestration of the occluding membrane in two). Three patients underwent membrane excision via a posterior fossa craniectomy. In the 26 patients who had undergone preoperative MR imaging, aqueductal patency was noted in 23 and aqueductal obstruction in three. These three patients underwent placement of a stent from the third ventricle to the posterior fossa cyst in addition to the ETV procedure. During the follow-up period, 12 patients with a CP shunt and four with a VP shunt experienced shunt malfunctions that required revision. Four patients with a CP shunt also required placement of a VP shunt. In addition, five of the 21 ETVs failed, requiring VP shunt insertion. A reduction in ventricle size noted on postoperative images occurred more frequently in patients with a VP shunt, whereas a reduction in cyst size was more appreciable in patients with a CP shunt. Successful ETV resulted in a slight decrease in ventricle size and varying degrees of reduction in cyst size. Endoscopic procedures may be considered an acceptable alternative in children with DWM. The authors propose a treatment protocol based on preoperative MR imaging findings of associated aqueductal stenosis.

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

PubMed Central

Garringer, Julie A.; Niyonkuru, Christian; McCullough, Emily H.; Loucks, Tammy; Dixon, C. Edward; Conley, Yvette P.; Berga, Sarah

2013-01-01

Abstract Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality (p=0.019) and better GOS-6 scores (p=0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone (p≤0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores (p≤0.05, all comparisons), and those with>1 risk SNP variant had a higher risk for poor outcome, compared with those with ≤1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI. PMID:23540392

Tension pneumocephalus following suboccipital sitting craniotomy in the pediatric population.

PubMed

Daszkiewicz, P; Dziedzic, D

Sitting craniotomy often results in entrapment of air in fluid-filled intracranial cavities. Gas under pressure exerts a deleterious effect on adjacent nervous tissue, resulting in clinical deterioration. To assess the incidence of tension pneumocephalus (TP) and to define risk factors associated therewith. Analysis included 100 consecutive patients (57 boys, 43 girls, mean age 9.7 y) undergoing suboccipital sitting craniotomy since 2012 to 2014. In our material (n=100) TP was seen in 7 cases, asymptomatic pneumocephalus (AP) in 77 and no pneumocephalus (NP) in 16. Tumor types encountered were typical for pediatric population. In the TP group (n=7) the ratio of low-grade to high-grade tumors was 5:2, in the AP group (n=77) 2:1 and in the NP group (n=16) 1:1. Preoperative hydrocephalus was present in 21 cases (21%, mean incidence), thereof 3 in the TP group (3/7; 42.8%), 12 in AP group (12/77; 15.5%) and 6 in the NP group (6/16; 37.5%). All TP patients received an emergency external drainage, thereof 4 required a permanent ventriculo-peritoneal shunt (57.1%), while AP and NP patients combined (n=93) required a permanent shunt in 4 cases only (4.3%). TP-associated morbidity (n=2) consisted in a significant deterioration of neurological condition. TP is a relatively rare but potentially serious complication of suboccipital sitting craniotomy. Risk factors for TP are low-grade tumor and pre-existing long-standing hydrocephalus. TP requires emergency decompression by temporary external drainage. TP patients significantly more often require a permanent CSF shunt. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes

PubMed Central

Samtani, Mahesh N; Raghavan, Nandini; Shi, Yingqi; Novak, Gerald; Farnum, Michael; Lobanov, Victor; Schultz, Tim; Yang, Eric; DiBernardo, Allitia; Narayan, Vaibhav A

2013-01-01

AIM The objective is to develop a semi-mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS-cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years. METHOD Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers. RESULTS CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B-test. CONCLUSION CSF biomarkers have the ability to discriminate MCI subjects into sub-populations that exhibit markedly different rates of disease progression on the ADAS-cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology. PMID:22534009

CPV cell characterization following one-year exposure in Golden Colorado

NASA Astrophysics Data System (ADS)

Bosco, Nick; Kurtz, Sarah

2014-09-01

A CPV module containing 30 III-V multijunction cells was operated on-sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to an off-sun event.

Timing of cranioplasty after decompressive craniectomy for ischemic or hemorrhagic stroke.

PubMed

Piedra, Mark P; Ragel, Brian T; Dogan, Aclan; Coppa, Nicholas D; Delashaw, Johnny B

2013-01-01

The optimal timing of cranioplasty after decompressive craniectomy for stroke is not known. Case series suggest that early cranioplasty is associated with higher rates of infection while delaying cranioplasty may be associated with higher rates of bone resorption. The authors examined whether the timing of cranioplasty after decompressive craniectomy for stroke affects postoperative complication rates. A retrospective cohort study was undertaken to evaluate complication rates in patients undergoing cranioplasty at early (within 10 weeks of craniectomy) or late (≥ 10 weeks) stages. Multivariate logistic regression analysis was used to determine characteristics that would predict complications in patients undergoing cranioplasty after decompressive craniectomy for stroke. While the overall complication rate was higher in the early cranioplasty cohort (22% vs 16% in the late cranioplasty cohort), the difference was not statistically significant (p = 0.5541). Patients in the early cranioplasty cohort had lower rates of postoperative hematoma but higher rates of infection. Presence of a CSF shunt was the only significant predictor of complications (OR 8.96, 95% CI 1.84-43.6). Complications rates for early cranioplasty (within 10 weeks of craniectomy) are similar to those encountered when cranioplasty is delayed, although the cohort size in this study was too small to state equivalence. Patients with a ventriculoperitoneal shunt are at higher risk for complications after cranioplasty.

Reversible ventriculoperitoneal shunt dysfunction and chronic constipation: case report.

PubMed

Morais, Barbara A; Cardeal, Daniel D; Andrade, Fernanda G; Paiva, Wellingson S; Matushita, Hamilton; Teixeira, Manoel J

2018-05-11

Constipation can cause transient malfunction of the ventriculoperitoneal shunt (VPS). Patients with myelomeningocele or cerebral palsy are often diagnosed with hydrocephalus and constipation due to neurogenic bowel. These patients are more prone to VPS dysfunction, often requiring surgical revision. The authors report the case of a 6-year-old girl with a VPS that had been implanted due to hydrocephalus secondary to myelomeningocele. The patient was brought to the emergency department with intermittent headache, vomiting, constipation, and abdominal distension and pain. A CT scan revealed ventricular dilatation and radiography of the abdomen showed bowel loop distension. After a Fleet enema and digital maneuvers, her abdominal distension and symptoms improved. A CT scan obtained 24 hours later showed a reduction in ventricular size. The mechanism by which constipation can lead to VPS malfunction can be traced to indirect increases of intraabdominal pressure and direct obstruction of the catheter by distended intestinal loops. Treating constipation can restore the free circulation of the CSF and avoid surgical intervention. Careful neurological monitoring of these patients is essential, because some measures used to treat constipation can increase intracranial pressure. The objective of this report was to highlight constipation as a possible cause of transient VPS malfunction, thereby avoiding unnecessary surgical revisions, to which children with hydrocephalus are frequently submitted.

The Effects of Hematopoietic Growth Factors on Neurite Outgrowth

PubMed Central

Su, Ye; Cui, Lili; Piao, Chunshu; Li, Bin; Zhao, Li-Ru

2013-01-01

Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF) production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity. PMID:24116056

Hydrocephalus shunt technology: 20 years of experience from the Cambridge Shunt Evaluation Laboratory.

PubMed

Chari, Aswin; Czosnyka, Marek; Richards, Hugh K; Pickard, John D; Czosnyka, Zofia H

2014-03-01

The Cambridge Shunt Evaluation Laboratory was established 20 years ago. This paper summarizes the findings of that laboratory for the clinician. Twenty-six models of valves have been tested long-term in the shunt laboratory according to the expanded International Organization for Standardization 7197 standard protocol. The majority of the valves had a nonphysiologically low hydrodynamic resistance (from 1.5 to 3 mm Hg/[ml/min]), which may result in overdrainage related to posture and during nocturnal cerebral vasogenic waves. A long distal catheter increases the resistance of these valves by 100%-200%. Drainage through valves without a siphon-preventing mechanism is very sensitive to body posture, which may result in grossly negative intracranial pressure. Siphon-preventing accessories offer a reasonable resistance to negative outlet pressure; however, accessories with membrane devices may be blocked by raised subcutaneous pressure. In adjustable valves, the settings may be changed by external magnetic fields of intensity above 40 mT (exceptions: ProGAV, Polaris, and Certas). Most of the magnetically adjustable valves produce large distortions on MRI studies. The behavior of a valve revealed during testing is of relevance to the surgeon and may not be adequately described in the manufacturer's product information. The results of shunt testing are helpful in many circumstances, such as the initial choice of shunt and the evaluation of the shunt when its dysfunction is suspected.

Deriving the Intrahepatic Arteriovenous Shunt Rate from CT Images and Biochemical Data Instead of from Arterial Perfusion Scintigraphy in Hepatic Arterial Infusion Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozaki, Toshiro, E-mail: ganronbun@amail.plala.or.jp; Seki, Hiroshi; Shiina, Makoto

2009-09-15

The purpose of the present study was to elucidate a method for predicting the intrahepatic arteriovenous shunt rate from computed tomography (CT) images and biochemical data, instead of from arterial perfusion scintigraphy, because adverse exacerbated systemic effects may be induced in cases where a high shunt rate exists. CT and arterial perfusion scintigraphy were performed in patients with liver metastases from gastric or colorectal cancer. Biochemical data and tumor marker levels of 33 enrolled patients were measured. The results were statistically verified by multiple regression analysis. The total metastatic hepatic tumor volume (V{sub metastasized}), residual hepatic parenchyma volume (V{sub residual};more » calculated from CT images), and biochemical data were treated as independent variables; the intrahepatic arteriovenous (IHAV) shunt rate (calculated from scintigraphy) was treated as a dependent variable. The IHAV shunt rate was 15.1 {+-} 11.9%. Based on the correlation matrixes, the best correlation coefficient of 0.84 was established between the IHAV shunt rate and V{sub metastasized} (p < 0.01). In the multiple regression analysis with the IHAV shunt rate as the dependent variable, the coefficient of determination (R{sup 2}) was 0.75, which was significant at the 0.1% level with two significant independent variables (V{sub metastasized} and V{sub residual}). The standardized regression coefficients ({beta}) of V{sub metastasized} and V{sub residual} were significant at the 0.1 and 5% levels, respectively. Based on this result, we can obtain a predicted value of IHAV shunt rate (p < 0.001) using CT images. When a high shunt rate was predicted, beneficial and consistent clinical monitoring can be initiated in, for example, hepatic arterial infusion chemotherapy.« less

Decreased head circumference in shunt-treated compared with healthy children.

PubMed

Nilsson, Daniel; Svensson, Johanna; Korkmaz, Betül A; Nelvig, Helena; Tisell, Magnus

2013-11-01

In this study, the authors' goal was to compare head circumference in hydrocephalic children during the first 4 years of ventriculoperitoneal (VP) shunt treatment with data on healthy children and to investigate predictors of skull growth in children with a VP shunt. Children from western Sweden treated for hydrocephalus with an initial VP shunt insertion performed between 2001 and 2006 who were younger than 12 months of age at the time of surgery were included. Children with major brain malformations, craniofacial syndromes, large cysts, and tumors were excluded. Head circumference, weight, and height at 9 defined ages up to 4 years were obtained and compared with data from a reference population of 3650 healthy children using the standard deviation score (SDS). Predictors (length, weight, etiology of hydrocephalus, valve type, number of revisions, valve setting, number of adjustments, and time of first surgery) for head circumference SDS and changes in head circumference SDS from shunt insertion at 1 year to last measurement were analyzed using bivariate and multiple linear regression analysis. Fifty children were included. The mean SDSs for head circumference in shunt-treated compared with healthy children were 1.95 ± 2.50 at shunt insertion (p < 0.001, n = 44), 0.38 ± 1.97 at 1 year (p = 0.27, n = 33), -0.96 ± 2.05 at 2 years (p = 0.046, n = 21), -1.39 ± 2.25 at 3 years (p = 0.026, n = 16), and 0.63 ± 3.34 at 4 years (p = 0.73, n = 4). Significant predictors for low head circumference SDS at 1 year of age were low weight (p = 0.002) and short height (p = 0.022) and at last measurement low weight (p < 0.0001), short height (p = 0.002), and 1-4 shunt revisions (p = 0.034). A significant predictor for change in head circumference SDS from shunt insertion to 1 year of age was the number of shunt valve revisions (p = 0.04) and at last measurement an etiology of intraventricular hemorrhage (p = 0.0058). Shunt-treated children have smaller head circumferences at 2 and 3 years of age than healthy children. Low weight, short height, etiology of intraventricular hemorrhage, and frequent shunt valve revisions are predictors for decreased head circumference. Prospective, randomized studies comparing skull growth using fixed and adjustable pressure-regulated shunt valves and flow-regulated valves are needed.

Current treatment of normal-pressure hydrocephalus: comparison of flow-regulated and differential-pressure shunt valves.

PubMed

Weiner, H L; Constantini, S; Cohen, H; Wisoff, J H

1995-11-01

FROM THE RECORDS of approximately 1500 shunt operations performed between 1987 and 1992, we identified 37 adults between ages 38 and 86 years (mean, 70 yr) with the normal-pressure hydrocephalus (NPH) syndrome who underwent surgery by a single surgeon. Since 1990, we have routinely used a flow-regulated shunt system (Orbis-Sigma valve [OSV]; Cordis Corporation, Miami, FL) in these patients. In this study, we compared the OSV system with conventional differential-pressure (DP) shunt systems uniformly used before 1990. This series (n = 37) consisted of 62% men (n = 23) and 38% women (n = 14). We excluded all patients with hydrocephalus associated with central nervous system neoplasms, intracerebral hemorrhage, or trauma as well those with radiographically documented late-onset aqueductal stenosis. All patients presented with the NPH clinical syndrome, chiefly with magnetic gait. In addition, 75% of patients experienced cognitive loss and 59% experienced urinary incontinence. The mean duration of preoperative symptoms was 35 months (range, 7-120 mo). Eight patients (22%) had undergone previous shunting procedures before referral to our service. A total of 89 shunt operations were performed in the 37 patients. Using actuarial methods and controlling for a history of prior shunt surgery, we found no significant difference in the time to initial malfunction (shunt survival) between the OSV and the DP shunts. There were three subdural hematomas and one infection in the OSV group compared with no complications in the DP valve group (P = 0.11). Thirty-six patients were available for follow-up, at a mean of 14 months after surgery. Nearly 90% of all patients experienced improvement in gait after shunting, regardless of the valve system that was used. There was one unrelated death. Realizing the limitations of a retrospective analysis and on the basis of the limited number of patients in this study, we conclude that using actuarial methods, we found no significant difference in shunt survival when comparing the OSV with the standard DP valve shunt systems with antisiphon devices in patients with NPH. Contrary to previous reports, the OSV is not free of overdrainage complications. Most patients (89%) with the NPH syndrome who primarily presented with gait disorder experienced significant improvement in gait after either OSV or DP shunting procedures when selected for surgery on the basis of the clinical syndrome and confirmatory radiographic data.

Prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with acute lymphoblastic leukaemia (ALL) treated without cranial irradiation: results of European Organization for Research and Treatment of Cancer (EORTC) Children Leukemia Group study 58881.

PubMed

Sirvent, Nicolas; Suciu, Stefan; Rialland, Xavier; Millot, Frédéric; Benoit, Yves; Plantaz, Dominique; Ferster, Alice; Robert, Alain; Lutz, Patrick; Nelken, Brigitte; Plouvier, Emmanuel; Norton, Lucilia; Bertrand, Yves; Otten, Jacques

2011-01-01

To evaluate the prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in the EORTC 58881 trial. Patients (2025) were categorised according to initial central nervous system (CNS) status: CNS-1 (CNS negative, n=1866), CNS-2 (<5 leucocytes/mm(3), CSF with blasts, n=50), CNS-3 (CNS positive, n=49), TLP+ (TLP with blasts, n=60). CNS-directed therapy consisted in intravenous (i.v.) methotrexate (5 g/sqm) in 4-10 courses, and intrathecal methotrexate injections (10-20), according to CNS status. Cranial irradiation was omitted in all patients. In the CNS1, TLP+, CNS2 and CNS3 group the 8-year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3% (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4% (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8-year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%), 10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a higher rate of initial bad risk features. Multivariate analysis indicated that presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii) for isolated and isolated or combined CNS relapse; WBC count<25 × 10(9)/L and Medac E-coli asparaginase treatment were each related to a lower CNS relapse risk. The presence of initial CNS involvement has no prognostic significance in EORTC 58881. Intensification of CNS-directed chemotherapy, without CNS radiation, is an effective treatment of initial meningeal leukaemic involvement. Copyright © 2010 Elsevier Ltd. All rights reserved.

GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

PubMed Central

McKenzie, Brent S.

2016-01-01

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD. PMID:27595596

CPV Cell Characterization Following One-Year Exposure in Golden, Colorado

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosco, Nick; Kurtz, Sarah

2014-09-26

A CPV module containing 30 III-V multijunction cells was operated on--sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to anmore » off-sun event.« less

CPV Cell Characterization Following One-Year Exposure in Golden, Colorado: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosco, N.; Kurtz, S.

2014-08-01

A CPV module containing 30 III-V multijunction cells was operated on?sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to anmore » off-sun event.« less

Prophylactic antibiotics in pediatric shunt surgery.

PubMed

Biyani, N; Grisaru-Soen, G; Steinbok, P; Sgouros, S; Constantini, S

2006-11-01

The optimal antibiotic prophylaxis for pediatric shunt-related procedures is not clear. There is much inconsistency among different medical centers. This paper summarizes and analyzes the various prophylactic antibiotic regiments used for shunt-related surgeries at different pediatric neurosurgery centers in the world. A survey questionnaire was distributed through the Pediatric Neurosurgery list-server (an e-mail-based special interest group in pediatric neurosurgery). Forty-five completed questionnaires were received, one per medical center, primarily from pediatric neurosurgeons with the following geographic breakdown: 25 from North America, 13 from Europe, and 7 from Asia and other countries. All centers routinely administered prophylactic antibiotics for shunt-related procedures. The drugs of choice were first-generation cephalosporins (23), second-generation cephalosporins (10), naficillin/oxacillin (4), vancomycin (3), clindamycin (1), amoxicillin (1), and mixed protocols in three centers. The initial drug administration ("first dose") was: in the department before transfer to operating room (5), upon arrival to operating room (11), at induction of anesthesia (13), and at initial skin incision (16). The duration of antibiotic dosage also varied: single dose (13), 24-h administration (26), 48-h administration (2), and longer than 48 h in four centers. Two general tendencies were noted, common to the majority of participating centers. There was a general trend to modify antibiotic treatment protocol in "high-risk" populations. The second common theme noted in more than half of responding centers was the use of long-term antibiotic treatment for externalized devices (such as externalized shunts, external ventricular drains or lumbar drains), usually till the device was in place.

Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

PubMed

Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

2003-12-01

We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

Management of idiopathic intracranial hypertension with a programmable lumboperitoneal shunt: Early experience.

PubMed

Alkherayf, Fahad; Abou Al-Shaar, Hussam; Awad, Michael

2015-09-01

To evaluate the clinical outcomes and complications rate among idiopathic intracranial hypertension (IIH) patients who underwent lumboperitoneal (LP) shunt insertion with a programmable Strata valve. We retrospectively evaluated patients who underwent LP shunt with a programmable Strata valve insertion at the University of Ottawa Civic Hospital from November 2012 to June 2013. The demographic data, clinical symptoms, opening pressure, pre-operative and post-operative visual fields, neuroimaging, visual acuity, disc status, and complications were recorded and analyzed. Seven female patients with IIH underwent insertion of an LP shunt with a programmable Strata valve. The mean opening pressure was 35.8 cm H2O. The initial valve setting was 1.5, and four patients required post-operative valve pressure adjustment. All patients showed significant improvement in objective visual testing at follow-up as well as less frequent headaches. None of the patients developed intra- or post-operative complications. LP shunts with programmable Strata valve systems are a potential alternative to conventional LP and programmable ventriculoperitoneal shunt systems as well as optic nerve sheath fenestration, due to their potential in avoiding brain injury, lower failure and complication rates, lower intracranial hypotension incidence, and flexibility in adjusting valve pressure settings post-operatively evading under- and overdrainage complications. They should be considered for the management of IIH instead of early design LP systems and VP shunts. A randomized multi-center trial should be conducted to compare the efficacy of these surgical techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

CSF Aβ1-42 - an excellent but complicated Alzheimer's biomarker - a route to standardisation.

PubMed

Kuhlmann, Julia; Andreasson, Ulf; Pannee, Josef; Bjerke, Maria; Portelius, Erik; Leinenbach, Andreas; Bittner, Tobias; Korecka, Magdalena; Jenkins, Rand G; Vanderstichele, Hugo; Stoops, Erik; Lewczuk, Piotr; Shaw, Leslie M; Zegers, Ingrid; Schimmel, Heinz; Zetterberg, Henrik; Blennow, Kaj

2017-04-01

The 42 amino acid form of amyloid β (Aβ 1 - 42 ) in cerebrospinal fluid (CSF) has been widely accepted as a central biomarker for Alzheimer's disease. Several immunoassays for CSF Aβ 1-42 are commercially available, but can suffer from between laboratory and batch-to-batch variability as well as lack of standardisation across assays. As a consequence, no general cut-off values have been established for a specific context of use (e.g., clinical diagnostics) and selection of individuals for enrolment in clinical trials (patient stratification) remains challenging. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has initiated a working group for CSF proteins (WG-CSF) to facilitate standardisation of CSF Aβ 1-42 measurement results. The efforts of the IFCC WG-CSF include the development of certified reference materials (CRMs) and reference measurement procedures (RMPs) for key biomarkers. Two candidate RMPs for quantification of Aβ 1-42 in CSF based on liquid chromatography tandem mass spectrometry have been developed and tested in two ring trials. Furthermore, two commutability studies including native CSF pools, artificial CSF and spiked materials have been completed. On the basis of these studies, human CSF pools containing only endogenous Aβ 1-42 at three concentrations were selected as the format for future CRMs that are now being processed. Copyright © 2016 Elsevier B.V. All rights reserved.

First 60 fetal in-utero myelomeningocele repairs at Saint Louis Fetal Care Institute in the post-MOMS trial era: hydrocephalus treatment outcomes (endoscopic third ventriculostomy versus ventriculo-peritoneal shunt).

PubMed

Elbabaa, Samer K; Gildehaus, Anne M; Pierson, Matthew J; Albers, J Andrew; Vlastos, Emanuel J

2017-07-01

The published results of the Management of Myelomeningocele Study (MOMS) trial in 2011 showed improved outcomes (reduced need for shunting, decreased incidence of Chiari II malformation, and improved scores of mental development and motor function) in the fetal prenatal repair group compared to the postnatal group. Historically, endoscopic third ventriculostomy (ETV) remains as a controversial hydrocephalus treatment option with high failure rates in pediatric patients with a history of myelomeningocele (MMC). We report hydrocephalus treatment outcomes in the fetal in-utero myelomeningocele repair patients who underwent repair at our Saint Louis Fetal Care Institute following the MOMS trial. We looked carefully at ETV outcomes in this patient population and we identified risk factors for failure. At our Saint Louis Fetal Care Institute, we followed the maternal and fetal inclusion and exclusion criteria used by the MOMS trial. The records of our first 60 fetal MMC repairs performed at our institute between 2011 and 2017 were examined. We retrospectively reviewed the charts, prenatal fetal magnetic resonance imaging (MRI) and ultrasound (US) imaging findings, postnatal brain MRI, and Bayley neurodevelopment testing results for infants and children who underwent surgical treatment of symptomatic hydrocephalus (VP shunt versus ETV). Multiple variables possibly related to ETV failure were considered for identifying risk factors for ETV failure. Between May 2011 and March 2017, 60 pregnant female patients underwent the prenatal MMC repair for their fetuses between 20 and 26 weeks' gestational age (GA) utilizing the standard hysterotomy for exposure of the fetus, and microsurgical repair of the MMC defect. All MMC defects underwent successful in-utero repair, with subsequent progression of the pregnancy. At the time of this study, 58 babies have been born, 56 are alive since there were 2 mortalities in the neonatal period due to prematurity. One patient was excluded given lack of consent for research purposes. From the remaining 55 patient included in this study, a total of 30 infants and toddlers underwent treatment of hydrocephalus (ETV and VPS groups). Twenty-five patients underwent ETV (24 primary ETV and 1 after shunt failure). Nineteen patients underwent shunt placements (6 primary/13 after ETV failure). Mean GA at time of MMC repair for the ETV group was 24 + 6/7 weeks (range 22 + 4/7 to 25 + 6/7). Mean follow up for patients who had a successful ETV was 17.25 months (range 4-57 months). Bayley neurodevelopmental testing results were examined pre- and post-ETV. Overall ETV success rate was 11/24 (45.8%) at the time of this study. The total number of patients who underwent shunt placement was 19/55 (34.5%), while shunting rate was 40% in the MOMS trial. Using a simple logistic regression analysis to identify predictors of ETV failure, ETV age ≤6 months and gestational age ≥23 weeks at repair of myelomeningocele were significant predictors for ETV failure while in-utero ventricular stability ≤4 mm and in-utero ventricular size post-repair ≤15.5 mm were significant predictors for ETV success. None of the listed variables independently predicted classification into ETV success versus ETV failure groups when entered into multiple logistic regression analysis. ETV, as an alternative to initial shunting, may continue to show promising results for treating fetal MMC repair patient population who present with symptomatic hydrocephalus during infancy and early childhood. Although our overall CSF diversion rate (ETV and VPS groups) in our fetal MMC group is higher than the MOMS trial, our shunting rate is lower given our higher incidence of patients with successful ETV. To our knowledge, this is the largest reported ETV series in patients who underwent fetal MMC repair. ETV deserves a closer look in the setting of improved hindbrain herniation in fetal in-utero MMC repair patients. In our series, young age (less than 6 months) and late GA at time of fetal MMC repair (after 23 weeks GA) were predictors for ETV failure, while in-utero stability of ventricular size (less than 4 mm) and in-utero ventricular size post-repair ≤15.5 mm were predictors for ETV success. Larger series and potential prospective randomized studies are required for further evaluation of risk factors for ETV failure in the fetal MMC patient population.

Establishment of the first international standard for PEGylated granulocyte colony stimulating factor (PEG-G-CSF): Report of an international collaborative study

PubMed Central

Wadhwa, Meenu; Bird, Chris; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian; Thorpe, Robin

2015-01-01

We assessed the feasibility of developing a suitable international reference standard for determination of in vitro biological activity of human sequence recombinant PEG-G-CSF products with a 20 kD linear PEG linked to the N-terminal methionyl residue of G-CSF (INN Filgrastim), produced using a conjugation process and coupling chemistry similar to that employed for the lead PEGfilgrastim product. Based on initial data which showed that the current WHO 2nd international standard, IS for G-CSF (09/136) or alternatively, a PEG-G-CSF standard with a unitage traceable to the G-CSF IS may potentially serve as the IS for PEG-G-CSF products, two candidate preparations of PEG-G-CSF were formulated and lyophilized at NIBSC. These preparations were tested by 23 laboratories using in vitro bioassays in a multi-centre collaborative study. Results indicated that on the basis of parallelism, the current WHO 2nd IS for G-CSF or any of the PEG-G-CSF samples could be used as the international standard for PEG-G-CSF preparations. However, because of the variability in potency estimates seen when PEG-G-CSF preparations were compared with the current WHO 2nd IS for G-CSF, a candidate PEG-G-CSF was suitable as the WHO IS. The preparation 12/188 was judged suitable to serve as the WHO IS based on in vitro biological activity data. Therefore, the preparation coded 12/188 was established by the WHO Expert Committee on Biological Standardization (ECBS) in 2013 as the WHO 1st IS for human PEGylated G-CSF with an assigned in vitro bioactivity of 10,000 IU per ampoule. PMID:25450254

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

PubMed Central

Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu; Bonkowski, Erin; Rowehl, Leahana; Krumsiek, Julia; Nix, Billy; Chalk, Claudia; Trapnell, Bruce; Zhu, Wei; Newberry, Rodney; Denson, Lee; Li, Ellen

2018-01-01

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. PMID:29434451

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis.

PubMed

Lind, Liza; Studahl, Marie; Persson Berg, Linn; Eriksson, Kristina

2017-07-10

The closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation. Secretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum. Most measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate. We show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.

Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs

PubMed Central

Tivers, Michael S.; Handel, Ian; Gow, Adam G.; Lipscomb, Victoria J.; Jalan, Rajiv; Mellanby, Richard J.

2015-01-01

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder. PMID:25658922

The reversibility of reduced cortical vein compliance in normal-pressure hydrocephalus following shunt insertion.

PubMed

Bateman, G A

2003-02-01

Superficial cortical venous compression secondary to alterations in craniospinal compliance is implicated in the pathogenesis of normal pressure hydrocephalus (NPH). A reduction in the pulsation in the outflow of the cortical veins would be expected to occur following compression of these veins and this has been shown in NPH. If cortical vein compression is a causative factor in NPH, it would be expected that cortical vein compliance as measured by pulsatility would be significantly altered by a curative procedure i.e. shunt tube insertion. My purpose is to compare the blood flow pulsatility characteristics in a group of patients with NPH before and after shunt tube insertion. I initially studied 18 subjects without pathology with MRI flow quantification studies of the cerebral arteries and veins to define the range of normality. The main study involved 18 patients with idiopathic dementia and mild leukoaraiosis who served as controls and seven patients with NPH studied before and after shunt insertion. Arterial, superior sagittal and straight sinus pulsatility was not significantly different between the patients with idiopathic dementia and those NPH patients before or after shunting. Cortical vein pulsatility before shunting in the patients with NPH was 43% lower than in those with idiopathic dementia ( P=0.006). Following shunting, cortical vein pulsatility increased by 186% ( P=0.007). There is thus reduced compliance in cortical veins in NPH which is significantly increased in patients who respond to insertion of a shunt tube. These findings suggest that reversible elevation in cortical vein pressure and reversal of the normal absorption pathway for cerebrospinal fluid may be behind the pathophysiology of NPH.

Endoscopic Third Ventriculostomy before Posterior Fossa Tumor Surgery in Adult Patients.

PubMed

Marx, Sascha; El Damaty, Ahmed; Manwaring, Jotham; El Refaee, Ehab; Fleck, Steffen; Fritsch, Michael; Gaab, Michael R; Schroeder, H W S; Baldauf, Jörg

2018-03-01

 Obstructive hydrocephalus in patients with posterior fossa tumors is frequently seen. Treatment options include immediate tumor removal or prior cerebrospinal fluid (CSF) diversion procedures. The necessity and feasibility of an ETV in these situations has not yet been proven in adult patients.  We retrospectively reviewed our prospectively maintained database for ETVs before surgery of posterior fossa tumors in adults. The primary focus of data analyses was the question of whether the ETV was suitable to treat the acute situation of hydrocephalus without an increased rate of complications due to the special anatomical situation with a posterior fossa tumor. We also analyzed whether any further CSF diverting procedures were necessary.  A total of 40 adult patients who underwent an ETV before posterior fossa tumor surgery were analyzed. Overall, 33 patients (82.5%) had clinical signs of hydrocephalus, and all of them improved in their clinical course after ETV. Seven patients (17.5%) did not demonstrate clinical signs of hydrocephalus, but ETV was performed with prophylactic or palliative intent in six patients and one patient, respectively. No complications were observed due to ETV itself. No permanent shunting procedure was necessary in a mean follow-up of 76.5 months. Early additional CSF diverting procedures (redo ETV, external ventricular drain) were performed in five patients (12.5%).  The present series confirms the feasibility and safety of ETV before posterior fossa tumor surgery in adult patients. If patients had symptomatic hydrocephalus before tumor surgery, an ETV can be performed, followed by early elective tumor surgery. A prophylactic ETV in asymptomatic patients is not advised. Early elective tumor surgery should be performed in these patients. Georg Thieme Verlag KG Stuttgart · New York.

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.

PubMed

Bardutzky, Jürgen; Witsch, Jens; Jüttler, Eric; Schwab, Stefan; Vajkoczy, Peter; Wolf, Stefan

2011-09-14

Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet. This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge. Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.

Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

PubMed Central

Silverberg, Gerald; Mayo, Martha; Saul, Thomas; Fellmann, Jere; McGuire, Dawn

2006-01-01

Background Abnormalities in cerebrospinal fluid (CSF) production and turnover, seen in normal pressure hydrocephalus (NPH) and in Alzheimer's disease (AD), may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP), consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for AD, excluding those with signs of concomitant NPH. Methods AD subjects by NINCDS-ADRDA criteria (n = 222), were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO2 of 40 Torr (40 mmHg). Results Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9%) enrolled in the study had CSFP of 220 mmH20 or greater, mean 249 ± 20 mmH20 which was significantly higher than 103 ± 47 mmH2O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS). Conclusion Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study. PMID:16737542

Impaired pulsation absorber mechanism in idiopathic normal pressure hydrocephalus: laboratory investigation.

PubMed

Park, Eun-Hyoung; Eide, Per Kristian; Zurakowski, David; Madsen, Joseph R

2012-12-01

The pathophysiology of normal pressure hydrocephalus (NPH), and the related problem of patient selection for treatment of this condition, have been of great interest since the description of this seemingly paradoxical condition nearly 50 years ago. Recently, Eide has reported that measurements of the amplitude of the intracranial pressure (ICP) can both positively and negatively predict response to CSF shunting. Specifically, the fraction of time spent in a "high amplitude" (> 4 mm Hg) state predicted response to shunting, which may represent a marker for hydrocephalic pathophysiology. Increased ICP amplitude might suggest decreased brain compliance, meaning a static measure of a pressure-volume ratio. Recent studies of canine data have shown that the brain compliance can be described as a frequency-dependent function. The normal canine brain seems to show enhanced ability to absorb the pulsations around the heart rate, quantified as a cardiac pulsation absorbance (CPA), with properties like a notch filter in engineering. This frequency dependence of the function is diminished with development of hydrocephalus in dogs. In this pilot study, the authors sought to determine whether frequency dependence could be observed in humans, and whether the frequency dependence would be any different in epochs with high ICP amplitude compared with epochs of low ICP amplitude. Systems analysis was applied to arterial blood pressure (ABP) and ICP waveforms recorded from 10 patients undergoing evaluations of idiopathic NPH to calculate a time-varying transfer function that reveals frequency dependence and CPA, the measure of frequency-dependent compliance previously used in animal experiments. The ICP amplitude was also calculated in the same samples, so that epochs with high (> 4 mm Hg) versus low (≤ 4 mm Hg) amplitude could be compared in CPA and transfer functions. Transfer function analysis for the more "normal" epochs with low amplitude exhibits a dip or notch in the physiological frequency range of the heart rate, confirming in humans the pulsation absorber phenomenon previously observed in canine studies. Under high amplitude, however, the dip in the transfer function is absent. An inverse relationship between CPA index and ICP amplitude is evident and statistically significant. Thus, elevated ICP amplitude indicates decreased performance of the human pulsation absorber. The results suggest that the human intracranial system shows frequency dependence as seen in animal experiments. There is an inverse relationship between CPA index and ICP amplitude, indicating that higher amplitudes may occur with a reduced performance of the pulsation absorber. Our findings show that frequency dependence can be observed in humans and imply that reduced frequency-dependent compliance may be responsible for elevated ICP amplitude observed in patients who respond to CSF shunting.

Time trends in utilization of G-CSF prophylaxis and risk of febrile neutropenia in a Medicare population receiving adjuvant chemotherapy for early-stage breast cancer.

PubMed

Goyal, Ravi K; Tzivelekis, Spiros; Rothman, Kenneth J; Candrilli, Sean D; Kaye, James A

2018-02-01

The purpose of this study is to assess temporal trends in the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis and risk of febrile neutropenia (FN) among older women receiving adjuvant chemotherapy for early-stage breast cancer. Women aged ≥ 66 years with diagnosis of early-stage breast cancer who initiated selected adjuvant chemotherapy regimens were identified using the SEER-Medicare data from 2002 to 2012. Adjusted, calendar-year-specific proportions were estimated for use of G-CSF primary prophylaxis (PP) and secondary prophylaxis and FN risk in the first and the second/subsequent cycles during the first course of chemotherapy, using logistic regression models. calendar-year-specific mean probabilities were estimated with covariates set to modal values. Among 11,107 eligible patients (mean age 71.7 years), 74% received G-CSF in the first course of chemotherapy. Of all patients, 5819 (52%) received G-CSF PP, and among those not receiving G-CSF PP, only 5% received G-CSF secondary prophylaxis. The adjusted proportion using G-CSF PP increased from 6% in 2002 to 71% in 2012. During the same period, the adjusted risk of FN in the first cycle increased from 2% to 3%; the adjusted risk increased from 1.5% to 2.9% among those receiving G-CSF PP and from 2.3% to 3.5% among those not receiving G-CSF PP. The use of G-CSF PP increased substantially during the study period. Although channeling of higher-risk patients to treatment with G-CSF PP is expected, the adjusted risk of FN among patients treated with G-CSF PP tended to be lower than among those not receiving G-CSF PP.

On-line process analysis innovation: DiComp (tm) shunting dielectric sensor technology

NASA Technical Reports Server (NTRS)

Davis, Craig R.; Waldman, Frank A.

1993-01-01

The DiComp Shunting Dielectric Sensor (SDS) is a new patent-pending technology developed under the Small Business Innovation Research Program (SBIR) for NASA's Kennedy Space Center. The incorporation of a shunt electrode into a conventional fringing field dielectric sensor makes the SDS uniquely sensitive to changes in material dielectric properties in the KHz to MHz range which were previously detectable only at GHz measurement frequencies. The initial NASA application of the SDS for Nutrient Delivery Control has demonstrated SDS capabilities for thickness and concentration measurement of Hoagland nutrient solutions. The commercial introduction of DiComp SDS technology for concentration and percent solids measurements in dispersions, emulsions and solutions represents a new technology for process measurements for liquids in a variety of industries.

Pulmonary Vein Doppler Patterns in Infants with Single Right Ventricle Anomalies After Initial Staged Palliations.

PubMed

Kirkpatrick, Edward C; Steltzer, Jessica; Simpson, Pippa; Pan, Amy; Dragulescu, Andrea; Falkensammer, Christine B; Gelehrter, Sarah; Lai, Wyman W; Levine, Jami; Miller, Stephen; Miller, Thomas A; Pruetz, Jay; Sachdeva, Ritu; Thacker, Deepika; Frommelt, Peter

2017-08-01

The aim of this study was to describe serial changes in echocardiographic Doppler pulmonary vein flow (PVF) patterns in infants with single right ventricle (RV) anomalies enrolled in the Single Ventricle Reconstruction trial. Measurement of PVF peak systolic (S) and diastolic (D) velocities, velocity time integrals (VTI), S/D peak velocity and VTI ratios, and frequency of atrial reversal (Ar) waves were made at three postoperative time points in 261 infants: early post-Norwood, pre-stage II surgery, and 14 months. Indices were compared over time, between initial shunt type [modified Blalock-Taussig shunt (MBTS) and right ventricle-to-pulmonary artery shunt (RVPAS)] and in relation to clinical outcomes. S velocities and VTI increased over time while D wave was stable, resulting in increasing S/D peak velocity and VTI ratios, with a median post-Norwood S/D VTI ratio of 1.14 versus 1.38 at pre-stage II and 1.89 at 14 months (P < 0.0001 between intervals). MBTS subjects had significantly higher S/D peak velocity and VTI ratios compared to RVPAS at the post-Norwood and pre-stage II time points (P < 0.0001) but not by 14 months. PVF patterns did not correlate with survival or hospitalization course at 1 year. PVF patterns after Norwood palliation differ from normal infants by having a dominant systolic pattern throughout infancy. PVF differences based upon shunt type resolve by 14 months and did not correlate with clinical outcomes. This study describes normative values and variations in PVF for infants with a single RV from shunt-dependent pulmonary blood flow to cavopulmonary blood flow.

Two Distinct Aerobic Methionine Salvage Pathways Generate Volatile Methanethiol in Rhodopseudomonas palustris

PubMed Central

Miller, Anthony R.; North, Justin A.; Wildenthal, John A.

2018-01-01

ABSTRACT 5′-Methyl-thioadenosine (MTA) is a dead-end, sulfur-containing metabolite and cellular inhibitor that arises from S-adenosyl-l-methionine-dependent reactions. Recent studies have indicated that there are diverse bacterial methionine salvage pathways (MSPs) for MTA detoxification and sulfur salvage. Here, via a combination of gene deletions and directed metabolite detection studies, we report that under aerobic conditions the facultatively anaerobic bacterium Rhodopseudomonas palustris employs both an MTA-isoprenoid shunt identical to that previously described in Rhodospirillum rubrum and a second novel MSP, both of which generate a methanethiol intermediate. The additional R. palustris aerobic MSP, a dihydroxyacetone phosphate (DHAP)-methanethiol shunt, initially converts MTA to 2-(methylthio)ethanol and DHAP. This is identical to the initial steps of the recently reported anaerobic ethylene-forming MSP, the DHAP-ethylene shunt. The aerobic DHAP-methanethiol shunt then further metabolizes 2-(methylthio)ethanol to methanethiol, which can be directly utilized by O-acetyl-l-homoserine sulfhydrylase to regenerate methionine. This is in contrast to the anaerobic DHAP-ethylene shunt, which metabolizes 2-(methylthio)ethanol to ethylene and an unknown organo-sulfur intermediate, revealing functional diversity in MSPs utilizing a 2-(methylthio)ethanol intermediate. When MTA was fed to aerobically growing cells, the rate of volatile methanethiol release was constant irrespective of the presence of sulfate, suggesting a general housekeeping function for these MSPs up through the methanethiol production step. Methanethiol and dimethyl sulfide (DMS), two of the most important compounds of the global sulfur cycle, appear to arise not only from marine ecosystems but from terrestrial ones as well. These results reveal a possible route by which methanethiol might be biologically produced in soil and freshwater environments. PMID:29636438

Predictors and outcomes of shunt-dependent hydrocephalus in patients with aneurysmal sub-arachnoid hemorrhage

PubMed Central

2012-01-01

Background Hydrocephalus following spontaneous aneurysmal sub-arachnoid hemorrhage (SAH) is often associated with unfavorable outcome. This study aimed to determine the potential risk factors and outcomes of shunt-dependent hydrocephalus in aneurysmal SAH patients but without hydrocephalus upon arrival at the hospital. Methods One hundred and sixty-eight aneurysmal SAH patients were evaluated. Using functional scores, those without hydrocephalus upon arrival at the hospital were compared to those already with hydrocephalus on admission, those who developed it during hospitalization, and those who did not develop it throughout their hospital stay. The Glasgow Coma Score, modified Fisher SAH grade, and World Federation of Neurosurgical Societies grade were determined at the emergency room. Therapeutic outcomes immediately after discharge and 18 months after were assessed using the Glasgow Outcome Score. Results Hydrocephalus accounted for 61.9% (104/168) of all episodes, including 82 with initial hydrocephalus on admission and 22 with subsequent hydrocephalus. Both the presence of intra-ventricular hemorrhage on admission and post-operative intra-cerebral hemorrhage were independently associated with shunt-dependent hydrocephalus in patients without hydrocephalus on admission. After a minimum 1.5 years of follow-up, the mean Glasgow outcome score was 3.33 ± 1.40 for patients with shunt-dependent hydrocephalus and 4.21 ± 1.19 for those without. Conclusions The presence of intra-ventricular hemorrhage, lower mean Glasgow Coma Scale score, and higher mean scores of the modified Fisher SAH and World Federation of Neurosurgical grading on admission imply risk of shunt-dependent hydrocephalus in patients without initial hydrocephalus. These patients have worse short- and long-term outcomes and longer hospitalization. PMID:22765765

High Risk of Dementia in Ventricular Enlargement with Normal Pressure Hydrocephalus Related Symptoms1.

PubMed

Koivisto, Anne M; Kurki, Mitja I; Alafuzoff, Irina; Sutela, Anna; Rummukainen, Jaana; Savolainen, Sakari; Vanninen, Ritva; Jääskeläinen, Juha E; Soininen, Hilkka; Leinonen, Ville

2016-03-22

Differential diagnosis of ventricular enlargement with normal pressure hydrocephalus (NPH) related symptoms is challenging. Patients with enlarged ventricles often manifest cognitive deterioration but their long-term outcome is not well known. We aim to evaluate long-term cognitive outcome in patients with enlarged ventricles and clinically suspected NPH. A neurologist and a neurosurgeon clinically evaluated 468 patients with enlarged ventricles and suspected NPH using radiological methods, intraventricular pressure monitoring, and frontal cortical brain biopsy. The neurologist confirmed final diagnoses after a median follow-up interval of 4.8 years. Altogether, 232 patients (50%) with enlarged ventricles did not fulfill the criteria for shunt surgery. The incidence of dementia among patients with enlarged ventricles, and at least one NPH-related symptom with adequate follow-up data (n = 446) was high, varying from 77 (iNPH, shunt responders) to 141/1000 person-years (non-shunted patients with enlarged ventricles). At the end of the follow-up, 59% of all these patients were demented. The demented population comprised 73% of non-shunted patients with enlarged ventricles, 63% of shunted iNPH patients that did not respond to treatment, and 46% of iNPH patients that were initially responsive to shunting. The most common cause of dementia was Alzheimer's disease (n = 94, 36%), followed by vascular dementia (n = 68, 26%). One-half of patients with enlarged ventricles and clinically suspected NPH were not shunted after intraventricular pressure monitoring. Dementia caused by various neurodegenerative diseases was frequently seen in patients with ventricular enlargement. Thus, careful diagnostic evaluation in collaboration with neurologists and neurosurgeons is emphasized.

Post-traumatic syringomyelia: CSF hydrodynamic changes following spinal cord injury are the driving force in the development of PTSM.

PubMed

Shields, Christopher B; Zhang, Yi Ping; Shields, Lisa B E

2012-01-01

Post-traumatic syringomyelia (PTSM) is a disorder that occurs infrequently following spinal cord injury (SCI), characterized by progressive neurological deterioration resulting from syrinx expansion originating in proximity to the traumatic epicenter. Several pathogenetic factors are associated with this disorder, however, the precise mechanism of the development of PTSM is controversial. Combined anatomical alterations and molecular changes following trauma to the spinal cord and arachnoid participate in the development of this condition. These factors include narrowing or obstruction of the subarachnoid space (SAS), central canal occlusion, myelomalacia, and alterations in intramedullary water permeability. If a patient sustains a SCI with delayed progressive deterioration in neurological function, in association with the MRI appearance of syringomyelia (SM), the diagnosis of PTSM is straightforward. The treatment of PTSM has not undergone any significant changes recently. The surgical treatment of PTSM consists of reconstructing the SAS or shunting fluid away from the syrinx to other locations. The advantages and disadvantages of each procedure will be discussed. With greater understanding of the mechanisms contributing to the development of SM, including advanced diagnostic methods and further advances in the development of artificial dural and shunting tubing, future therapies of PTSM will be more effective and long-lasting. Incorporation of alterations of AQP4 expression provides an intriguing possibility for future treatment of PTSM. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model

PubMed Central

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration. PMID:26376304

Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

PubMed

Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

2015-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

[Clinical, epidemiological, and etiological studies of adult aseptic meningitis: a report of 12 cases of herpes simplex meningitis, and a comparison with cases of herpes simplex encephalitis].

PubMed

Himeno, Takahiro; Shiga, Yuji; Takeshima, Shinichi; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

2018-01-26

We treated 437 cases of adult aseptic meningitis and 12 cases (including 2 recurrent patients; age, 31.8 ± 8.9 years; 7 females) of herpes simplex meningitis from 2004 to 2016. The incidence rate of adult herpes simplex meningitis in the cases with aseptic meningitis was 2.7%. One patient was admitted during treatment of genital herpes, but no association was observed between genital herpes and herpes simplex meningitis in the other cases. The diagnoses were confirmed in all cases as the cerebrospinal fluid (CSF) was positive for herpes simplex virus (HSV)-DNA. For diagnosis confirmation, the DNA test was useful after 2-7 days following initial disease onset. Among other types of aseptic meningitis, the patients with herpes simplex meningitis showed relatively high white blood cell counts and relatively high CSF protein and high CSF cell counts. CSF cells showed mononuclear cell dominance from the initial stage of the disease. During same period, we also experienced 12 cases of herpes simplex encephalitis and 21 cases of non-hepatic acute limbic encephalitis. Notably, the patients with herpes simplex meningitis were younger and their CSF protein and cells counts were higher than those of the patients with herpes simplex encephalitis.

Unrecognised ventriculitis/meningitis presenting as hydrocephalus in infancy.

PubMed

Udani, Vrajesh; Udani, Soonu; Merani, Rohan; Bavdekar, Manisha

2003-09-01

Infantile hydrocephalus due to unrecognized neonatal-onset meningitis/ventriculitis, was studied retrospectively using 1991-1998 chart review. Seventy two patients with hydrocephalus were reviewed. Thirteen infants had hydrocephalus associated with active meningitis/ventriculitis which had remained unrecognized. Active meningitis/ventriculitis was confirmed by the finding of an abnormal lumbar and ventricular CSF with or without positive culture. All had perinatal risk factors and 10/13 had been given antibiotics in the postnatal period. 6/13 infants appeared to be well. The most common presentation was increasing head size. All lumbar and ventricular CSFs were abnormal and 10/13 had positive cultures as well. Imaging revealed hydrocephalus in all. The infants were treated with antibiotics for a mean of 32.8 days before VP shunting. 7/11 were severely disabled. Unrecognized active meningitis/ventriculitis is an important cause of infantile hydrocephalus.

Headaches secondary to intraventricular silicone oil successfully managed with ventriculoperitoneal shunt.

PubMed

Hruby, Paul M; Poley, Preeti R; Terp, Patricia A; Thorell, William E; Margalit, Eyal

2013-01-01

To describe a case of intravitreal silicone oil (SO) migration into the cerebral ventricles with secondary chronic headaches. Retrospective case report. Chart review. Single patient. A 51-year-old man with a history of proliferative diabetic retinopathy underwent surgery for traction retinal detachment using SO. Postoperatively, he developed elevated intraocular pressure, headaches, and a blind painful eye, which was enucleated. Neuroimaging revealed SO within the cerebral ventricles. Five years after the initial retinal detachment surgery, the patient developed chronic headaches. Lumbar puncture revealed an elevated opening pressure. The headaches were initially managed medically. A ventriculoperitoneal shunt was placed after the headaches persisted, which resulted in their complete resolution at 6 weeks after shunt placement. Ocular hypertension after intravitreal SO placement may play a role in SO intracranial migration. In the case presented, intraventricular SO was the apparent cause of elevated intracranial pressure and headaches. As all published cases of intraventricular SO migration reporting intraocular pressure to this point have described ocular hypertension, careful monitoring of intraocular pressure and aggressive control of ocular hypertension in the presence of intravitreal SO is recommended.

Hepatoblastoma in Children With Congenital Portosystemic Shunts.

PubMed

Lautz, Timothy B; Shah, Sonam A; Superina, Riccardo A

2016-04-01

Two children developed hepatoblastoma concurrent with congenital portosystemic shunts (PSSs) (Abernethy malformations). Both underwent operative ligation of their PSSs. One received concurrent tumor resection, whereas the other was deemed initially unresectable and underwent biopsy followed by neoadjuvant chemotherapy. Although benign hepatic masses, such as focal nodular hyperplasia and nodular regenerative hyperplasia, are common in patients with Abernethy malformations, malignant tumors have also been documented and should always be considered in the differential diagnosis of a patient with a congenital PSS and a hepatic mass.

Phase-contrast cerebrospinal fluid flow magnetic resonance imaging in qualitative evaluation of patency of CSF flow pathways prior to infusion of chemotherapeutic and other agents into the fourth ventricle.

PubMed

Patel, Rajan P; Sitton, Clark W; Ketonen, Leena M; Hou, Ping; Johnson, Jason M; Romo, Seferino; Fletcher, Stephen; Shah, Manish N; Kerr, Marcia; Zaky, Wafik; Rytting, Michael E; Khatua, Soumen; Sandberg, David I

2018-03-01

Nuclear medicine studies have previously been utilized to assess for blockage of cerebrospinal fluid (CSF) flow prior to intraventricular chemotherapy infusions. To assess CSF flow without nuclear medicine studies, we obtained cine phase-contrast MRI sequences that assess CSF flow from the fourth ventricle down to the sacrum. In three clinical trials, 18 patients with recurrent malignant posterior fossa tumors underwent implantation of a ventricular access device (VAD) into the fourth ventricle, either with or without simultaneous tumor resection. Prior to infusing therapeutic agents into the VAD, cine MRI phase-contrast CSF flow sequences of the brain and total spine were performed. Velocity encoding (VENC) of 5 and 10 cm/s was used to confirm CSF flow from the fourth ventricular outlets to the cervical, thoracic, and lumbar spine. Qualitative CSF flow was characterized by neuroradiologists as present or absent. All 18 patients demonstrated CSF flow from the outlets of the fourth ventricle down to the sacrum with no evidence of obstruction. One of these patients, after disease progression, subsequently showed obstruction of CSF flow. No patient required a nuclear medicine study to assess CSF flow prior to initiation of infusions. Fourteen patients have received infusions to date, and none has had neurological toxicity. CSF flow including the fourth ventricle and the total spine can be assessed noninvasively with phase-contrast MRI sequences. Advantages over nuclear medicine studies include avoiding both an invasive procedure and radiation exposure.

CSF beta-amyloid 1–42 – what are we measuring in Alzheimer's disease?

PubMed Central

Hu, William T; Watts, Kelly D; Shaw, Leslie M; Howell, Jennifer C; Trojanowski, John Q; Basra, Sundeep; Glass, Jonathan D; Lah, James J; Levey, Allan I

2015-01-01

Objective To characterize biological and technical factors which influence cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, including the presence of apolipoprotein E (APOE) ε4 allele, AD diagnosis, Aβ-binding proteins, sample processing, and preanalytical handling. Methods CSF was collected from 140 subjects with normal cognition, mild cognitive impairment, AD, and non-AD dementia. CSF levels of beta-amyloid 1–42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) were analyzed following the standard and modified protocols. CSF levels of apoJ, apoE, albumin, and α-synuclein were measured in a subgroup (n = 69), and their effects on measured AD biomarker levels were also determined in vitro using human CSF samples. Results CSF Aβ42 levels measured using the AD Neuro-imaging Initiative (ADNI) protocol (which we call suspended Aβ42 or susAβ) were lower than total measurable CSF Aβ42 in all groups, and on average represents 57% of the latter. Logistic regression analysis showed this proportion (% susAβ) to be directly correlated with CSF Aβ42 and apoJ levels, but inversely correlated with CSF t-Tau levels. Finally, we showed in vitro that increasing apoE and apoJ levels directly increased % susAβ. Conclusion CSF susAβ levels are influenced by biological and technical factors, and may represent a marker of Aβ susceptible to lipoprotein-mediated clearance. Clinical trials should include total measurable Aβ42 and susAβ to better inform outcomes. PMID:25750918

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

Endoscopic third ventriculostomy and posterior fossa tumors.

PubMed

Di Rocco, Federico; Jucá, Carlos Eduardo; Zerah, Michel; Sainte-Rose, Christian

2013-02-01

The management of hydrocephalus associated with a posterior fossa tumor is debated. Some authors emphasize the advantages of an immediate tumor removal that may normalize the cerebrospinal fluid (CSF) dynamics. However, in clinical practice, the mere excision of the lesion has been demonstrated to be accompanied by a persisting hydrocephalus in about one third of the cases. Preoperative endoscopic third ventriculostomy (ETV) offers several advantages. It may control the intracranial pressure (ICP), avoid the necessity of an emergency procedure, allow appropriate scheduling of the operation for tumor removal, and eliminate the risks related to the presence of an external drainage. The procedure also reduces the incidence of postoperative hydrocephalus. A final advantage, more difficult to weight, but obvious to the neurosurgeon, is the possibility to remove the lesion with a relaxed brain and normal ICP. In the postoperative phase, ETV can be used in case of persisting hydrocephalus, both in patients who underwent only the excision of the tumor and in those whose preoperative ETV failed as a consequence of intraventricular bleeding with secondary closure of the stoma (redoETV). The main advantage of postoperative ETV is that the procedure is carried out only in case of persisting hydrocephalus; its use is consequently more selective than preoperative ETV. The disadvantage consists in the common use of an external CSF drainage in the first few postoperative days, which is necessary to control the pressure and for ruling out those cases that reach a spontaneous cure of the hydrocephalus. The authors review the criteria for patient selection and the results of ETV performed in case of hydrocephalus secondary to a posterior fossa tumor. Preoperative ETV constitutes an effective procedure for controlling the hydrocephalus associated with posterior fossa tumors. It might lower the rate of persistent postoperative hydrocephalus and result in a short hospital stay. Low rates of patients requiring an extrathecal-CSF shunt device are also reported by authors who utilize ETV postoperatively. As, however, the assessment of the persistent hydrocephalus in these children is based on prolonged ICP monitoring through an external CSF drainage, their results are weighted by a major risk of infective complications and longer hospital stay. Copyright © 2013 Elsevier Inc. All rights reserved.

Morbidity of repeat transsphenoidal surgery assessed in more than 1000 operations.

PubMed

Jahangiri, Arman; Wagner, Jeffrey; Han, Sung Won; Zygourakis, Corinna C; Han, Seunggu J; Tran, Mai T; Miller, Liane M; Tom, Maxwell W; Kunwar, Sandeep; Blevins, Lewis S; Aghi, Manish K

2014-07-01

OBJECT.: While transsphenoidal surgery is associated with low morbidity, the degree to which morbidity increases after reoperation remains unclear. The authors determined the morbidity associated with repeat versus initial transsphenoidal surgery after 1015 consecutive operations. The authors conducted a 5-year retrospective review of the first 916 patients undergoing transsphenoidal surgery at their institution after a pituitary center of expertise was established, and they analyzed morbidities. The authors analyzed 907 initial and 108 repeat transsphenoidal surgeries performed in 916 patients (9 initial surgeries performed outside the authors' center were excluded). The most common diagnoses were endocrine inactive (30%) or active (36%) adenomas, Rathke's cleft cysts (10%), and craniopharyngioma (3%). Morbidity of initial surgery versus reoperation included diabetes insipidus ([DI] 16% vs 26%; p = 0.03), postoperative hyponatremia (20% vs 16%; p = 0.3), new postoperative hypopituitarism (5% vs 8%; p = 0.3), CSF leak requiring repair (1% vs 4%; p = 0.04), meningitis (0.4% vs 3%; p = 0.02), and length of stay ([LOS] 2.8 vs 4.5 days; p = 0.006). Of intraoperative parameters and postoperative morbidities, 1) some (use of lumbar drain and new postoperative hypopituitarism) did not increase with second or subsequent reoperations (p = 0.3-0.9); 2) some (DI and meningitis) increased upon second surgery (p = 0.02-0.04) but did not continue to increase for subsequent reoperations (p = 0.3-0.9); 3) some (LOS) increased upon second surgery and increased again for subsequent reoperations (p < 0.001); and 4) some (postoperative hyponatremia and CSF leak requiring repair) did not increase upon second surgery (p = 0.3) but went on to increase upon subsequent reoperations (p = 0.001-0.02). Multivariate analysis revealed that operation number, but not sex, age, pathology, radiation therapy, or lesion size, increased the risk of CSF leak, meningitis, and increased LOS. Separate analysis of initial versus repeat transsphenoidal surgery on the 2 most common benign pituitary lesions, pituitary adenomas and Rathke's cleft cysts, revealed that the increased incidence of DI and CSF leak requiring repair seen when all pathologies were combined remained significant when analyzing only pituitary adenomas and Rathke's cleft cysts (DI, 13% vs 35% [p = 0.001]; and CSF leak, 0.3% vs 9% [p = 0.0009]). Repeat transsphenoidal surgery was associated with somewhat more frequent postoperative DI, meningitis, CSF leak requiring repair, and greater LOS than the low morbidity characterizing initial transsphenoidal surgery. These results provide a framework for neurosurgeons in discussing reoperation for pituitary disease with their patients.

Incidence and persistence of classical swine fever in free-ranging wild boar (Sus scrofa).

PubMed

Rossi, S; Fromont, E; Pontier, D; Crucière, C; Hars, J; Barrat, J; Pacholek, X; Artois, M

2005-06-01

Although veterinary authorities aim to limit persistence of classical swine fever (CSF) in wild boar (Sus scrofa), to avoid potential transmission to pigs, factors influencing CSF transmission and persistence are not clearly understood. Here we analyse incidence and persistence in a CSF epidemic that occurred in the French Vosges Forest. Higher incidence was found in large forests compared to smaller isolated ones, being highest near the starting point of the epidemic, but poorly related to the local density. We hypothesize that the spatial and social structure of wild boar populations may be responsible for this variability of incidence over space. Persistence was highest near the starting point of the epidemic and where initial density was highest. We hypothesize that persistence was favoured by the abundance of young wild boar, itself encouraged by CSF. Our results allow us to propose management measures aimed at limiting CSF persistence.

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

PubMed

Giulieri, S; Chapuis-Taillard, C; Jaton, K; Cometta, A; Chuard, C; Hugli, O; Du Pasquier, R; Bille, J; Meylan, P; Manuel, O; Marchetti, O

2015-10-01

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

Serial MRI and CSF biomarkers in normal aging, MCI, and AD

PubMed Central

Vemuri, P.; Wiste, H.J.; Weigand, S.D.; Knopman, D.S.; Trojanowski, J.Q.; Shaw, L.M.; Bernstein, M.A.; Aisen, P.S.; Weiner, M.; Petersen, R.C; Jack, C.R

2010-01-01

Objective: To compare the annual change in MRI and CSF biomarkers in cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer disease (AD). Comparisons were based on intergroup discrimination, correlation with concurrent cognitive/functional changes, relationships to APOE genotype, and sample sizes for clinical trials. Methods: We used data from the Alzheimer's Disease Neuroimaging Initiative study consisting of CN, aMCI, and AD cohorts with both baseline and 12-month follow-up CSF and MRI. The annual change in CSF (total-tau [t-tau], Aβ1-42) and MRI (change in ventricular volume) was obtained in 312 subjects (92 CN, 149 aMCI, 71 AD). Results: There was no significant average annual change in either CSF biomarker in any clinical group except t-tau in CN; moreover, the annual change did not differ by clinical group in pairwise comparisons. In contrast, annual increase in ventricular volume increased in the following order, AD > aMCI > CN, and differences were significant between all clinical groups in pairwise comparisons. Ventricular volume increase correlated with concurrent worsening on cognitive/functional indices in aMCI and AD whereas evidence of a similar correlation with change in CSF measures was unclear. The annual changes in MRI differed by APOE ε4 status overall and among aMCI while annual changes in CSF biomarkers did not. Estimated sample sizes for clinical trials are notably less for MRI than the CSF or clinical measures. Conclusions: Unlike the CSF biomarkers evaluated, changes in serial structural MRI are correlated with concurrent change on general cognitive and functional indices in impaired subjects, track with clinical disease stage, and are influenced by APOE genotype. GLOSSARY AD = Alzheimer disease; ADAS-Cog = Alzheimer's Disease Assessment Scale–cognitive subscale; ADNI = Alzheimer's Disease Neuroimaging Initiative; aMCI = amnestic mild cognitive impairment; AUROC = area under the receiver operator characteristic curve; BSI = boundary shift integral; CDR-SB = Clinical Dementia Rating–sum of boxes; CN = cognitively normal; MMSE = Mini-Mental State Examination; NFT = neurofibrillary tangle; NT = neuropil thread; PiB = Pittsburgh compound B; t-tau = total-tau. PMID:20625167

Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease

PubMed Central

Zetterberg, Henrik; Mattsson, Niklas; Johansson, Per; Minthon, Lennart; Blennow, Kaj; Olsson, Mattias

2015-01-01

Objective: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). Methods: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. Results: The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93–0.94). The best PET measures performed similarly (AUC 0.92–0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03–0.12, p < 0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. Conclusions: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. Classification of evidence: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately. PMID:26354982

Hydrocephalus treatment in children: long-term outcome in 975 consecutive patients.

PubMed

Beuriat, Pierre-Aurelien; Puget, Stephanie; Cinalli, Giuseppe; Blauwblomme, Thomas; Beccaria, Kevin; Zerah, Michel; Sainte-Rose, Christian

2017-07-01

OBJECTIVE Hydrocephalus remains one of the more common pathologies managed in pediatric neurosurgical units. Endoscopic third ventriculostomy (ETV) has an advantage over ventriculoperitoneal shunting as it enables patients to remain device free. Multiple shunt devices with various valve designs exist, with no one valve proven to be superior to another. The aim of this study was to describe the management of hydrocephalus and its long-term outcome. METHODS The authors retrospectively reviewed the medical records of all patients who had been treated for hydrocephalus at the Hôpital Necker-Enfants Malades in the period from 1985 to 1995. RESULTS Nine hundred seventy-five children had been treated for hydrocephalus. The mean follow-up was 11 ± 7.4 years (mean ± standard deviation). The most common cause of hydrocephalus was tumor related (32.3%), followed by malformative (24.5%) and inflammatory (20.9%) causes. Two hundred eighty patients underwent ETV as the first-line treatment. The procedure was effective in controlling hydrocephalus due to posterior fossa tumors and aqueductal stenosis. Six hundred ninety-five children had initial shunt insertion, with the majority receiving an Orbis-Sigma valve (OSV). The overall OSV shunt survival was 70% at 1 year, 58% at 10 years, and 49% at 20 years. The most common cause for mechanical shunt failure was obstruction (50.7%). Overall shunt survival was statistically different between the OSV and the differential-pressure valve (p = 0.009). CONCLUSIONS Endoscopic third ventriculostomy is effective in the management of childhood hydrocephalus. Its success is directly related to the underlying pathology. In the long term, the OSV has significantly higher event-free shunt survival than the classic differential-pressure valve systems.

Venous Shunt Versus Venous Ligation for Vascular Damage Control: The Immunohistochemical Evidence.

PubMed

Góes Junior, Adenauer Marinho de Oliveira; Abib, Simone de Campos Vieira; Alves, Maria Teresa de Seixas; Ferreira, Paulo Sérgio Venerando da Silva; Andrade, Mariseth Carvalho de

2017-05-01

To evaluate the expression of immunohistochemical markers of tissue ischemia (iNOS, eNOS, and HSP70) in a vascular damage control experimental model to determine if a venous temporary vascular shunt insertion leads to a better limb perfusion when compared with the ligature of the injured vein. Experimental study in male Sus Scrofa weighting 40 Kg. Animals were distributed into 5 groups: group 1 animals were submitted to right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2 animals were submitted to right EIA shunting and right EIV shunting; group 3 animals were submitted to right EIV ligation; group 4 animals were submitted to right EIV shunting; group 5 animals were not submitted to vascular shunting or venous ligation. Transonic Systems flowmeters were used to measure vascular flow on right and left external iliac vessels, and i-STAT (Abbot) portable blood analyzer was used for EIVs blood biochemical analysis. An initial baseline register of invasive arterial pressure, iliac vessels flow, and venous blood analysis was performed. Arterial pressure and iliac vessels flow were taken immediately after right iliac vessels shunting or ligation. Then, hemorrhagic shock was induced by continuous 20 mL/min blood withdraw from the external right jugular vein whereas arterial blood pressure and iliac vessels flow registers were taken every 10 min, and blood samples from EIVs were obtained every 30 min until the vascular flow through right EIA (or through the shunt inserted into the right EIV for group 4 animals) became inexistent or until the animal's death. After the end of the experiments, bilateral hind limb's biopsies were obtained for immunohistochemical analysis. Using image editing and analysis software, the expression of iNOS, eNOS, and HSP70 (3 well-known ischemic associated immunohistochemical markers) was assessed. The mean expression of each marker in the right hind limb was compared between groups. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. Immunohistochemical analysis showed no difference regarding the iNOS expression; nevertheless, both eNOS and HSP70 expression were statistically more intense (P < 0.05) on group 1 (eNOS = 1.32; HSP70 = 15.05) than on group 2 (eNOS = 0.018; HSP70 = 8.56). The higher expression of eNOS and HSP70 in the right hind limbs of group 1 animals (arterial shunt and venous ligature) than group 2 animals (arterial shunt and venous shunt) suggests that venous ligation is associated with more intense ischemic histological findings than venous shunting. Copyright © 2017 Elsevier Inc. All rights reserved.

[Disproportionately large communicating fourth ventricle--report of 2 cases].

PubMed

Matsumoto, M; Kushida, Y; Shibata, I; Seiki, Y; Terao, H

1983-11-01

A term of 'disproportionately large, communicating fourth ventricle' (DLCFV) was first proposed by in Harwood-Nash in 1980. It is somewhat different from the well known clinical entity of 'isolated or trapped fourth ventricle', because of apparent patency of aqueductal canal. Two cases of typical DLCFV encountered in our clinic were described. First patient was a 24 year old man in whom this condition developed following operations for lumber disc and second patient was 22 year old woman in whom the disease developed after subarachnoid hemorrhage. In both cases, main symptoms were attributable to hydrocephalus but three posterior fossa symptoms, nystagmus, Parinaud' sign and truncal ataxia were also characteristic. On the CT scan, the fourth ventricle was extraordinarily enlarged. Patency of the aqueductal canal was demonstrated by air study or Conray and Metrizamide ventriculography. On the other hand, occlusion was demonstrated or highly suspected in or near the foramina Magendie and Luschka. After a routine ventriculo-peritoneal shunt operation, the fourth ventricle decreased in size and the symptoms were immediately relieved. Plausible explanation for mechanism involved in occurrence of DLCFV were (1) occlusion process in or near the fourth ventricle outlets seems to be crucial in this pathologic condition. Collision of CSF pulse waves against the obstruction may yield a water hammer effect on the fourth ventricle. (2) abnormal weakness of the brain stem parenchyma around the fourth ventricle to CSF pressure may be another contributory factor.

Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting

PubMed Central

Fisher, N; McCafferty, I; Dolapci, M; Wali, M; Buckels, J; Olliff, S; Elias, E

1999-01-01

BACKGROUND—The role of percutaneous hepatic vein angioplasty in the management of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our unit, we have often used this technique in cases of short length hepatic vein stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse hepatic vein occlusion or failed angioplasty. 
AIMS—To review the outcome of angioplasty and surgical shunting to define their respective roles. 
PATIENTS—All patients treated by angioplasty or surgical shunting for non-malignant hepatic vein obstruction over a ten year period from 1987 to 1996. 
METHODS—A case note review of pretreatment features and clinical outcome. 
RESULTS—Angioplasty was attempted in 21 patients with patent hepatic vein branches and was succesful in 18; in three patients treatment was unsuccessful and these patients had surgical shunts. Fifteen patients were treated by surgical shunting only. Mortality according to definitive treatment was 3/18 following angioplasty and 8/18 following surgery; in most cases this reflected high risk status prior to treatment. Venous or shunt reocclusion rates were similar for both groups and were associated with subtherapeutic warfarin in half of these cases. Most surviving patients in both groups are asymptomatic although one surgical patient has chronic hepatic encephalopathy. 
CONCLUSION—With appropriate case selection, many patients with Budd-Chiari syndrome caused by short length hepatic vein stenosis or occlusion may be managed successfully by angioplasty alone. Medium term outcome is good following this procedure provided that anticoagulation is maintained. Further follow up is required to assess for definitive benefits but we suggest that this should be included as a valid initial approach in the algorithm for management of Budd-Chiari syndrome. 

 Keywords: Budd-Chiari syndrome; short length hepatic vein stenosis; hepatic vein occlusion; percutaneous hepatic vein angioplasty; mesocaval shunt PMID:10075967

Frequency of Alzheimer's disease pathology at autopsy in patients with clinical normal pressure hydrocephalus.

PubMed

Cabral, Danielle; Beach, Thomas G; Vedders, Linda; Sue, Lucia I; Jacobson, Sandra; Myers, Kent; Sabbagh, Marwan N

2011-09-01

Normal pressure hydrocephalus (NPH) is considered to be potentially treatable with the placement of a cerebrospinal fluid (CSF) shunt. However, the procedure has been reported to have variable success, particularly with respect to improving the cognitive impairment in NPH. The presence of neurologic comorbidities, particularly Alzheimer's disease (AD), may contribute to shunt responsiveness. Uncovering the extent to which AD and NPH co-occur has implications for diagnosis and treatment of NPH. Autopsy studies of patients with NPH during their lifetime would elucidate the frequency of such comorbidities. A search of the Sun Health Research Institute Brain Donation Program database was conducted between January 1, 1997 and April 1, 2009 to identify all cases with neuropathologic evidence of dementia as well as those of clinically diagnosed NPH. We reviewed the medical records and brain findings of each NPH case. Of the 761 cases autopsied over the study interval, 563 were found to have neuropathologic evidence meeting criteria for a dementing illness. Of 563 cases, AD was found exclusively in 313 (56%), and 94 suffered from secondary diagnosis of dementia. Nine of 761 cases were identified with a clinical diagnosis of NPH, which were among the 563 cases with neuropathology of dementing illness at autopsy, representing 1.6% (9/563) of the cases. On review of brain autopsy reports of these nine patients, eight (89%) were found to have AD and one (11%) had progressive supranuclear palsy. Review of the medical records of the nine NPH cases revealed the following clinical comorbidities: five suffered from AD, one from Parkinson's Disease, one from mild cognitive impairment, and one from seizure disorder. Given the findings of the present study, we support the AD-NPH theory and posit that AD is a common pathologic comorbidity in the setting of NPH and may preclude cognitive improvement postshunt placement. This may influence the selection of cases for shunting in the future. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Case of Mycobacterium tuberculosis meningitis: Gram staining as a useful initial diagnostic clue for tuberculous meningitis.

PubMed

Kawakami, Sayoko; Kawamura, Yasuyosi; Nishiyama, Kyouhei; Hatanaka, Hiroki; Fujisaki, Ryuichi; Ono, Yasuo; Miyazawa, Yukihisa; Nishiya, Hajime

2012-12-01

A 32-year-old man was admitted to our hospital because of fever, headache, and loss of consciousness. Four days before admission, he had had difficulty speaking. On the day of admission, his colleague had found him to be unconscious and lying on his back. He was admitted to our hospital. The temperature at the eardrum was 35.2°C. Neurologic evaluation was negative. Computed tomography (CT) scan of the brain showed slight ventricular enlargement bilaterally. An X-ray film of the chest showed no abnormality. On the second hospital day, neck stiffness was noted. The cerebrospinal fluid (CSF) contained 870 white cells/μl, most of which were neutrophils; the glucose level in the CSF was 10 mg/dl, and the protein level was 140 mg/dl. Stained smears of the CSF, including Gram staining and India-ink preparations, disclosed no microorganisms. Capsular antigen tests for several bacteria were negative. Antimicrobial agents were started. However, by changing the microscope focus slightly while viewing Gram stains of the CSF, we could see brightened and Gram-positive bacilli that had been phagocytosed by neutrophils. This finding suggested the presence of Mycobacterium tuberculosis. Ziehl-Neelsen staining of the CSF and gastric juice revealed anti-acid bacilli. Polymerase chain reaction for M. tuberculosis in the gastric juice was positive. This case showed that Gram staining could be useful as an initial adjunct for the diagnosis of tuberculous meningitis, particularly when the CSF shows predominantly neutrocytic pleocytosis, but no other evidence of bacterial meningitis.

The Soldier Fitness Tracker: Global Delivery of Comprehensive Soldier Fitness

ERIC Educational Resources Information Center

Fravell, Mike; Nasser, Katherine; Cornum, Rhonda

2011-01-01

Carefully implemented technology strategies are vital to the success of large-scale initiatives such as the U.S. Army's Comprehensive Soldier Fitness (CSF) program. Achieving the U.S. Army's vision for CSF required a robust information technology platform that was scaled to millions of users and that leveraged the Internet to enable global reach.…

Cerebrospinal fluid drainage for syringomyelia.

PubMed

Williams, B; Sgouros, S; Nenji, E

1995-12-01

Twenty-eight years of experience with syringomyelia of various causes in the syringomyelia clinic at the Midland Centre for Neurosurgery and Neurology has provided a database of 723 patients, mostly adults, with either hindbrain herniation, syringomyelia or both. Treatment of syringomyelia by drainage has never been the optimum primary treatment on the basis that the cavity is usually secondary to some other disturbance of the cerebrospinal fluid pathways. Over this period 73 patients had either syrinx drainage (56 syringopleural, 14 syringo-subarachnoid shunts) or other procedure such as myelotomy and cord transection. Ten years after operation only 53.5% and 50% of these two groups respectively continued to remain clinically stable. A complication rate of 15.7% included fatal haemorrhage, infection and displacement of drains. At second operation or necropsy at least 5% of shunts were found to be blocked. All the shunts were inserted without a valve and the lowering of the intrasyrinx pressure has therefore been energetic when the lower end of the drainage tube has been taken to the pleural or peritoneal cavities. This produced collapse of the cord cavities around the tip of the drainage tube and increased the likelihood of blockage. If the mechanisms which were responsible for the syringomyelia were still operative then recurrence was likely to occur alongside the drainage tube leaving the tube immured in the wall of the syrinx cavity. When hydrocephalus was present, in addition treatment of the hydrocephalus by a valved shunt to the peritoneum or to the right atrium was often effective in improving the syringomyelia. This treatment has also been used in patients without hydrocephalus. The mechanisms of improvement were unclear but this treatment stratagem has nevertheless been employed in 45 cases. In 30 out of these 45 cases the drainage of cerebrospinal fluid from outside the syrinx cavities seemed to be worthwhile; 10 patients suffered some form of complication, most of which were reversible; 8 patients were worse following surgery. It is concluded that both drainage of the syringomyelia cavity and also extra-syrinx drainage may have a place in the management of difficult syringomyelia problems although the primary treatment should be to establish the patency of CSF pathways in both hindbrain-related and non-hindbrain-related cases.

Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

NASA Astrophysics Data System (ADS)

Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

2012-06-01

Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

PubMed

Barni, S; Lorusso, V; Giordano, M; Sogno, G; Gamucci, T; Santoro, A; Passalacqua, R; Iaffaioli, V; Zilembo, N; Mencoboni, M; Roselli, M; Pappagallo, G; Pronzato, P

2014-01-01

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long-term analysis of the ALFA-9802 GM-CSF study.

PubMed

Thomas, Xavier; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cecile; de Botton, Stephane; Terre, Christine; Gardin, Claude; Hayette, Sandrine; Preudhomme, Claude; Dombret, Herve

2010-04-01

: Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase-specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance complete remission (CR) rate and event-free survival (EFS) in younger adults with acute myeloid leukemia (AML). : In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM-CSF concurrently with all cycles of chemotherapy. The effects of GM-CSF on survival were reported herein with a long-term follow-up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers. : The EFS rate was better in the GM-CSF group (43% vs 34%; P = .04). GM-CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM-CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3-ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM-CSF priming, the difference in terms of EFS was highly significant (5-year EFS, 39% with GM-CSF vs 8% without GM-CSF; P = .007). : Sensitization of leukemic cells and their progenitors by GM-CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor-prognosis FLT3-ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. (c) 2010 American Cancer Society.

Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem Cell Transplantation: Comparison of Two Practices.

PubMed

Singh, Amrita D; Parmar, Sapna; Patel, Khilna; Shah, Shreya; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Phillips, Adrienne; Hsu, Jing-Mei; Niesvizky, Ruben; Mark, Tomer M; Pearse, Roger; Rossi, Adriana; van Besien, Koen

2018-02-01

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5 × 10 9 /L (ANC-driven). G-CSF was dosed at 300 µg in patients weighing <75 kg and 480 µg in those weighing ≥75 kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P < .0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P < .0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival. Published by Elsevier Inc.

Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

PubMed Central

Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

2018-01-01

Abstract Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Methods Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Results Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. Conclusions To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection. PMID:29401308

Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

PubMed

Burbelo, Peter D; Price, Richard W; Hagberg, Lars; Hatano, Hiroyu; Spudich, Serena; Deeks, Steven G; Gisslén, Magnus

2018-03-13

Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P > .0001) and blood antibodies by 7-fold (P = .0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.

The role of diffusion tensor imaging and fractional anisotropy in the evaluation of patients with idiopathic normal pressure hydrocephalus: a literature review.

PubMed

Siasios, Ioannis; Kapsalaki, Eftychia Z; Fountas, Kostas N; Fotiadou, Aggeliki; Dorsch, Alexander; Vakharia, Kunal; Pollina, John; Dimopoulos, Vassilios

2016-09-01

OBJECTIVE Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention. METHODS The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: "Alzheimer's disease," "brain," "cerebrospinal fluid," "CSF," "diffusion tensor imaging," "DTI," "hydrocephalus," "idiopathic," "magnetic resonance imaging," "normal pressure," "Parkinson's disease," and "shunting." Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles. RESULTS The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers. CONCLUSIONS Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.

Sarcocystis neurona-specific immunoglobulin G in the serum and cerebrospinal fluid of horses administered S neurona vaccine.

PubMed

Witonsky, Sharon; Morrow, Jennifer K; Leger, Clare; Dascanio, John; Buechner-Maxwell, Virginia; Palmer, Wally; Kline, Kristen; Cook, Anne

2004-01-01

A vaccine against Sarcocystis neurona, which induces equine protozoal myeloencephalitis (EPM), has received conditional licensure in the United States. A major concern is whether the immunoglobulin G (IgG) response elicited by the vaccine will compromise the use of Western blotting (WB) as a diagnostic tool in vaccinated horses with neurologic disease. Our goals were to determine if vaccination (1) causes seroconversion: (2) causes at least a transient increase in S neurona-specific IgG in the cerebrospinal fluid (CSF); and (3) induces an IgG response that can be differentiated from that induced by natural exposure. Horses included in the study (n = 29) were older than 6 months with no evidence of neurologic disease. The presence or absence of anti-S neurona antibodies in the serum of each horse was determined by WB analysis. Seropositive horses had CSF collected and submitted for cytology, CSF index, and WB analysis. The vaccine was administered to all the horses and boostered 3-4 weeks later. On day 14 after the 2nd administration, serum and CSF were collected and analyzed. Eighty-nine percent (8 of 9) of the initial seronegative horses seroconverted after vaccination, of which 57% (4 of 7) had anti-S neurona IgG in their CSE Eighty percent (16 of 20) of the seropositive horses had an increase in serum S neurona IgG after vaccination. Of the 6 of 20 horses that were initially seropositive/CSF negative, 2 were borderline positive for anti-S neurona IgG in the CSF, 2 tested positive, and 2 were excluded because the CSF sample had been contaminated by blood. There were no WB banding patterns that distinguished samples from horses that seroconverted due to vaccination versus natural exposure. Caution must be used in interpreting WB analysis from neurologic horses that have been recently vaccinated for EPM.

The Structure of the GM-CSF Receptor Complex Reveals a Distinct Mode of Cytokine Receptor Activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Guido; Hercus, Timothy R.; McClure, Barbara J.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific {alpha} subunit and a {beta}c subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface andmore » functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.« less

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice

PubMed Central

Almenar Cubells, D; Bosch Roig, C; Jiménez Orozco, E; Álvarez, R; Cuervo, JM; Díaz Fernández, N; Sánchez Heras, AB; Galán Brotons, A; Giner Marco, V; Codes M De Villena, M

2013-01-01

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004–2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2–11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1–8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7–5.4) and higher response rate (OR: 2.1, 95%CI: 1.2–3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice. PMID:23331323

Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

PubMed

Mollenhauer, Brit; Caspell-Garcia, Chelsea J; Coffey, Christopher S; Taylor, Peggy; Shaw, Leslie M; Trojanowski, John Q; Singleton, Andy; Frasier, Mark; Marek, Kenneth; Galasko, Douglas

2017-11-07

To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF Aβ42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. α-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/Aβ42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF α-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF α-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

PubMed

Constantinescu, R; Krýsl, D; Bergquist, F; Andrén, K; Malmeström, C; Asztély, F; Axelsson, M; Menachem, E B; Blennow, K; Rosengren, L; Zetterberg, H

2016-04-01

Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability. © 2016 EAN.

Relationship between intracranial pressure and antifungal agents levels in the CSF of patients with cryptococcal meningitis.

PubMed

Wirth, Fernanda; de Azevedo, Maria Isabel; Pilla, Carmen; Aquino, Valério Rodrigues; Neto, Gustavo Wissmann; Goldani, Luciano Zubaran

2018-04-01

The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5΄flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.

Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

PubMed Central

Caspell-Garcia, Chelsea J.; Coffey, Christopher S.; Taylor, Peggy; Shaw, Leslie M.; Trojanowski, John Q.; Singleton, Andy; Frasier, Mark; Marek, Kenneth; Galasko, Douglas

2017-01-01

Objective: To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. Methods: CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1–42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. Results: CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF Aβ42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. α-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/Aβ42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale motor scores or dopamine imaging. CSF α-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. Conclusions: These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF α-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD. PMID:29030452

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.

2012-03-20

Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91more » CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.« less

The cerebrospinal fluid proteome in HIV infection: change associated with disease severity

PubMed Central

2012-01-01

Background Central nervous system (CNS) infection is a nearly universal feature of untreated systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. Results After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral therapy and correlated abundances of identified proteins a) within and between subjects, b) with all other proteins across the entire sample set, and c) with "external" CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) ≤ -0.3 and ≥0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Conclusions Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases. PMID:22433316

Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

PubMed

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2014-01-01

Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

Detection of cerebrospinal fluid leakage: initial experience with three-dimensional fast spin-echo magnetic resonance myelography.

PubMed

Tomoda, Y; Korogi, Y; Aoki, T; Morioka, T; Takahashi, H; Ohno, M; Takeshita, I

2008-03-01

The pathogenesis of cerebrospinal fluid (CSF) hypovolemia is supposed to be caused by CSF leakage through small dural defects. To compare source three-dimensional (3D) fast spin-echo (FSE) images of magnetic resonance (MR) myelography with radionuclide cisternography findings, and to evaluate the feasibility of MR myelography in the detection of CSF leakage. A total of 67 patients who were clinically suspected of CSF hypovolemia underwent indium-111 radionuclide cisternography, and 27 of those who had direct findings of CSF leakage were selected for evaluation. MR myelography with 3D FSE sequences (TR/TE 6000/203 ms) was performed at the lumbar spine for all patients. We evaluated source images and maximum intensity projection (MIP) images of MR myelography, and the findings were correlated with radionuclide cisternography findings. MR myelography of five healthy volunteers was used as a reference. The MR visibility of the CSF leakage was graded as definite (leakage clearly visible), possible (leakage poorly seen), or absent (not shown). CSF leakage was identified with source 3D FSE images in 22 (81.5%) of 27 patients. Of the 22 patients, 16 were graded as definite and six were graded as possible. For the definite cases, 3D FSE images clearly showed the extent of the leaked CSF in the paraspinal structures. In the remaining five patients with absent findings, radionuclide cisternography showed only slight radionuclide activity out of the arachnoid space. Source 3D FSE images of MR myelography seem useful in the detection of CSF leakage. Invasive radionuclide cisternography may be reserved for equivocal cases only.

Adapting Certified Safe Farm to North Carolina Agriculture: An Implementation Study.

PubMed

Storm, Julia F; LePrevost, Catherine E; Tutor-Marcom, Robin; Cope, W Gregory

2016-01-01

Certified Safe Farm (CSF) is a multimodal safety and health program developed and assessed through multiple controlled intervention studies in Iowa. Although developed with the intent to be broadly applicable to agriculture, CSF has not been widely implemented outside the midwestern United States. This article describes the CSF implementation process in North Carolina (NC), as piloted on a large-scale in three agriculturally diverse and productive counties of NC, and reports its effectiveness using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. Implementation involved (1) capacity building through safety and health training, (2) adaptation of components of Iowa's CSF model to NC agriculture, (3) marketing and recruitment, and (4) formative evaluation, including an online survey and focus group discussion. From 2009 to 2012, 113 farms participated in at least one component of the CSF intervention, representing a NC farm participation rate of 3.1% in the study area. A major adaptation of NC implementation was the utilization of NC Cooperative Extension as the local driver of implementation in contrast to local AgriSafe clinics in Iowa. The most innovative adaptation to CSF components was the development of a defined economic incentive in the form of a cost-share program. The RE-AIM framework was found to be useful and relevant to the field of agricultural health and safety translational research. This study provides effectiveness measures and implementation alternatives useful for those considering implementing CSF. It informs current efforts to move CSF from research to practice through the National Sustainable Model CSF Program initiative.

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

PubMed Central

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2015-01-01

Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

Risk factors for unplanned readmission within 30 days after pediatric neurosurgery: a nationwide analysis of 9799 procedures from the American College of Surgeons National Surgical Quality Improvement Program

PubMed Central

Sherrod, Brandon A.; Johnston, James M.; Rocque, Brandon G.

2017-01-01

Objective Readmission rate is increasingly used as a quality outcome measure after surgery. The purpose of this study was to establish, using a national database, the baseline readmission rates and risk factors for readmission after pediatric neurosurgical procedures. Methods The American College of Surgeons National Surgical Quality Improvement Program–Pediatric database was queried for pediatric patients treated by a neurosurgeon from 2012 to 2013. Procedures were categorized by current procedural terminology code. Patient demographics, comorbidities, preoperative laboratory values, operative variables, and postoperative complications were analyzed via univariate and multivariate techniques to find associations with unplanned readmission within 30 days of the primary procedure. Results A total of 9799 cases met the inclusion criteria, 1098 (11.2%) of which had an unplanned readmission within 30 days. Readmission occurred 14.0 ± 7.7 days postoperatively (mean ± standard deviation). The 4 procedures with the highest unplanned readmission rates were CSF shunt revision (17.3%), repair of myelomeningocele > 5 cm in diameter (15.4%), CSF shunt creation (14.1%), and craniectomy for infratentorial tumor excision (13.9%). Spine (6.5%), craniotomy for craniosynostosis (2.1%), and skin lesion (1.0%) procedures had the lowest unplanned readmission rates. On multivariate regression analysis, the odds of readmission were greatest in patients experiencing postoperative surgical site infection (SSI; deep, organ/space, superficial SSI and wound disruption: OR > 12 and p < 0.001 for each). Postoperative pneumonia (OR 4.294, p < 0.001), urinary tract infection (OR 4.262, p < 0.001), and sepsis (OR 2.616, p = 0.006) also independently increased the readmission risk. Independent patient risk factors for unplanned readmission included Native American race (OR 2.363, p = 0.019), steroid use > 10 days (OR 1.411, p = 0.010), oxygen supplementation (OR 1.645, p = 0.010), nutritional support (OR 1.403, p = 0.009), seizure disorder (OR 1.250, p = 0.021), and longer operative time (per hour increase, OR 1.059, p = 0.014). Conclusions This study may aid in identifying patients at risk for unplanned readmission following pediatric neurosurgery, potentially helping to focus efforts at lowering readmission rates, minimizing patient risk, and lowering costs for health care systems. PMID:27184348

Risk factors for unplanned readmission within 30 days after pediatric neurosurgery: a nationwide analysis of 9799 procedures from the American College of Surgeons National Surgical Quality Improvement Program.

PubMed

Sherrod, Brandon A; Johnston, James M; Rocque, Brandon G

2016-09-01

OBJECTIVE Hospital readmission rate is increasingly used as a quality outcome measure after surgery. The purpose of this study was to establish, using a national database, the baseline readmission rates and risk factors for patient readmission after pediatric neurosurgical procedures. METHODS The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was queried for pediatric patients treated by a neurosurgeon between 2012 and 2013. Procedures were categorized by current procedural terminology (CPT) code. Patient demographics, comorbidities, preoperative laboratory values, operative variables, and postoperative complications were analyzed via univariate and multivariate techniques to find associations with unplanned readmissions within 30 days of the primary procedure. RESULTS A total of 9799 cases met the inclusion criteria, 1098 (11.2%) of which had an unplanned readmission within 30 days. Readmission occurred 14.0 ± 7.7 days postoperatively (mean ± standard deviation). The 4 procedures with the highest unplanned readmission rates were CSF shunt revision (17.3%; CPT codes 62225 and 62230), repair of myelomeningocele > 5 cm in diameter (15.4%), CSF shunt creation (14.1%), and craniectomy for infratentorial tumor excision (13.9%). The lowest unplanned readmission rates were for spine (6.5%), craniotomy for craniosynostosis (2.1%), and skin lesion (1.0%) procedures. On multivariate regression analysis, the odds of readmission were greatest in patients experiencing postoperative surgical site infection (SSI; deep, organ/space, superficial SSI, and wound disruption: OR > 12 and p < 0.001 for each). Postoperative pneumonia (OR 4.294, p < 0.001), urinary tract infection (OR 4.262, p < 0.001), and sepsis (OR 2.616, p = 0.006) also independently increased the readmission risk. Independent patient risk factors for unplanned readmission included Native American race (OR 2.363, p = 0.019), steroid use > 10 days (OR 1.411, p = 0.010), oxygen supplementation (OR 1.645, p = 0.010), nutritional support (OR 1.403, p = 0.009), seizure disorder (OR 1.250, p = 0.021), and longer operative time (per hour increase, OR 1.059, p = 0.029). CONCLUSIONS This study may aid in identifying patients at risk for unplanned readmission following pediatric neurosurgery, potentially helping to focus efforts at lowering readmission rates, minimizing patient risk, and lowering costs for health care systems.

[Concentration of tazobactam/piperacillin in the cerebrospinal fluid of patients with Haemophilus influenzae type B meningitis].

PubMed

Fukasawa, Chie; Hoshino, Tadashi; Kutsuna, Satoru; Sawada, Kyoko; Sato, Hiroko; Ishiwada, Naruhiko

2013-09-01

While the incidence of Haemophilus influenzae type b (Hib) meningitis is expected to decrease with the widespread use of the Hib vaccine, the resistance of Hib has actually increased. Therefore, selection of the initial antibiotics used for treatment must be performed with resistant bacteria, including beta-lactamase negative ampicillin resistant H. influenzae (BLNAR), in mind. Tazobactam/piperacillin (TAZ/PIPC) has a satisfactory minimum inhibitory concentration (MIC) against BLNAR and is a beta-lactamase inhibitor. Although there is no insurance coverage for its use in patients with meningitis, the penetration of TAZ/PIPC into cerebrospinal fluid (CSF) in animal experiments promises a satisfactory result, and we have been using a combination of ceftriaxone (CTRX) and TAZ/PIPC as an initial treatment and a resistant bacteria countermeasure in patients with Hib meningitis at our hospital since 2008. We examined the concentration of TAZ/PIPC in CSF to further investigate the possibility of using TAZ/PIPC as an antibiotic treatment against bacterial meningitis. In cases treated with a 1: 8 drug formulation of TAZ/PIPC against Hib meningitis at our hospital, we used the remaining portion of a CSF sample collected after the initiation of TAZ/PIPC administration and then measured the concentrations of TAZ and PIPC in the CSF. Six specimens from 5 patients between the ages of 6 and 59 months were examined. The dosage of TAZ/PIPC was 95.7-113.6 mg/kg/dose x 3 times/day, and the CSF concentrations at 0-105 minutes after the completion of the administration were 0.319-1.32 microg/mL for TAZ and 2.54-7.74 microg/mL for PIPC. With the approved dosage, the peak concentration level during the acute period indicated a sufficient CSF concentration level for the antibacterial and beta-lactamase inhibition effects against Hib. As an antibiotic treatment for H. influenzae meningitis, the combined usage of TAZ/PIPC is likely to be effective as a resistant bacteria countermeasure, in addition to third-generation cephem drugs and meropenem.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

PubMed Central

Peluso, Michael J.; Valcour, Victor; Ananworanich, Jintanat; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L. K.; Lerdlum, Sukalya; Chomchey, Nitiya; Slike, Bonnie; Sailasuta, Napapon; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2015-01-01

Background. It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Methods. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Results. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = −0.40; P = .03), frontal white matter (r = −0.46; P = .01), and parietal gray matter (r = −0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = −0.51; P = .02) and parietal gray matter (r = −0.46; P = .04). Conclusions. CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health. PMID:25995196

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

PubMed Central

Peluso, Michael J.; Valcour, Victor; Phanuphak, Nittaya; Ananworanich, Jintanat; Fletcsher, James LK; Chalermchai, Thep; Krebs, Shelly J.; Robb, Merlin L.; Hellmuth, Joanna; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2018-01-01

Objective To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. Design Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. Methods AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow up on cART in a subset of these individuals (6 months in AHI participants [n=24], 1 year in CHI participants [n=10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Results Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/L; p=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, p=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, p=0.011), and neurofilament light chain (r=0.56, p=0.0008) in CSF. Conclusions This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI. PMID:27819802

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection.

PubMed

Peluso, Michael J; Valcour, Victor; Phanuphak, Nittaya; Ananworanich, Jintanat; Fletcher, James L K; Chalermchai, Thep; Krebs, Shelly J; Robb, Merlin L; Hellmuth, Joanna; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2017-01-14

To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. AHI (n = 33) and CHI (n = 34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n = 24), 1 year in CHI participants (n = 10)]. Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/l; P = 0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/l; P = 0.003). In untreated CHI, YKL-40 correlated with neopterin (r = 0.51, P = 0.0025), chemokine (CXC-motif) ligand-10 (r = 0.44, P = 0.011), and neurofilament light chain (r = 0.56, P = 0.0008) in CSF. This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection.

PubMed

Peluso, Michael J; Valcour, Victor; Ananworanich, Jintanat; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L K; Lerdlum, Sukalya; Chomchey, Nitiya; Slike, Bonnie; Sailasuta, Napapon; Gisslén, Magnus; Zetterberg, Henrik; Spudich, Serena

2015-12-01

It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04). CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In vitro performance of the fixed and adjustable gravity-assisted unit with and without motion-evidence of motion-induced flow.

PubMed

Kimura, Takaoki; Schulz, Matthias; Shimoji, Kazuaki; Miyajima, Masakazu; Arai, Hajime; Thomale, Ulrich-Wilhelm

2016-10-01

Anti-siphon devices and gravitational-assisted valves have been introduced to counteract the effects of overdrainage after implantation of a shunt system. The study examined the flow performance of two gravitational-assisted valves (shunt assistant - SA and programmable shunt assistant - proSA, Miethke & Co. KG, Potsdam, Germany) in an in vitro shunt laboratory with and without motion. An in vitro laboratory setup was used to model the cerebrospinal fluid (CSF) drainage conditions similar to a ventriculo-peritoneal shunt and to test the SA (resistance of +20 cmH2O in 90°) and proSA (adjustable resistance of 0 to +40 cmH2O in 90°). The differential pressure (DP) through the simulated shunt and tested valve was adjusted between 0 and 60 cmH2O by combinations of different inflow pressures (40, 30, 20, 10, and 0 cmH2O) and the hydrostatic negative outflow pressure (0, -20, and -40 cmH2O) in several differing device positions (0°, 30°, 60°, and 90°). In addition, the two devices were tested under vertical motion with movement frequencies of 2, 3, and 4 Hz. Both gravity-assisted units effectively counteract the hydrostatic effect in relation to the chosen differential pressure. The setting the proSA resulted in flow reductions in the 90° position according to the chosen resistance of the device. Angulation-related flow changes were similar in the two devices in 30-90° position, however, in the 0-30° position, a higher flow is seen in the proSA. Repeated vertical movement significantly increased flow through both devices. While with the proSA a 2-Hz motion was not able to induce additional flow (0.006 ± 0.05 ml/min), 3- and 4-Hz motion significantly induced higher flow values (3 Hz: +0.56 ± 0.12 ml/min, 4 Hz: +0.54 ± 0.04 ml/min). The flow through the SA was not induced by vertical movements at a low DP of 10 cmH2O at all frequencies, but at DPs of 30 cmH2O and higher, all frequencies significantly induced higher flow values (2 Hz: +0.36 ± 0.14 ml/min, 3 Hz: +0.32 ± 0.08 ml/min, 4 Hz: +0.28 ± 0.09 ml/min). In a static setup, both tested valves effectively counteracted the hydrostatic effect according to their adjusted or predefined resistance in vertical position. Motion-induced increased flow was demonstrated for both devices with different patterns of flow depending on applied DP and setting of the respective valve. The documented increased drainage should be considered when selecting appropriate valves and settings in very active patients.

EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines. In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet. Methods/Design This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge. Discussion Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage. Trial registration www.clinicaltrials.gov Identifier: NCT01258257 PMID:21917146

Introduction of percutaneous-tunneled transfontanellar external ventricular drainage in the management of hydrocephalus in extremely low-birth-weight infants.

PubMed

Zucchelli, Mino; Lefosse, Mariella; Corvaglia, Luigi; Martini, Silvia; Sandri, Fabrizio; Soffritti, Silvia; Ancora, Gina; Mammoliti, Palma; Gargano, Giancarlo; Galassi, Ercole

2016-07-01

OBJECTIVE Hydrocephalus treatment in extremely low-birth-weight (ELBW) infants still represents a challenge for the pediatric neurosurgeon, particularly when the patient weighs far less than 1000 g. In such cases, the benefits in terms of neurological outcome following early treatment do not always outweigh the surgical risks, especially considering the great difference in the surgical risk before patient weight increases. To assess the efficacy and reliability of a percutaneous-tunneled, transfontanellar external ventricular drain (PTTEVD) in ELBW infants, the authors started a new protocol for the early surgical treatment of hydrocephalus. METHODS Ten cases of posthemorrhagic hydrocephalus (PHH) in ELBW infants (5 cases < 700 g, range for all cases 550-1000 g) were treated with a PTTEVD that was implanted at bedside as the first measure in a stepwise approach. RESULTS The average duration of the procedure was 7 minutes, and there was no blood loss. The drain remained in place for an average of 24 days (range 8-45 days). In all cases early control of the hydrocephalus was achieved. One patient had a single episode of CSF leakage (due to insufficient CSF removal). In another patient Enterococcus in the CSF sample was detected the day after abdominal surgery with ileostomy (infection resolved with intrathecal vancomycin). One patient died of Streptococcus sepsis, a systemic infection existing prior to drain placement that never resolved. One patient had Pseudomonas aeruginosa sepsis prior to drain insertion; a PTTEVD was implanted, the infection resolved, and the hydrocephalus was treated in the same way as with a traditional EVD, while the advantages of a quick, minimally invasive, bedside procedure were maintained. Once a patient reached 1 kg in weight, when necessary, a ventriculoperitoneal shunt was implanted and the PTTEVD was removed. CONCLUSIONS The introduction of PTTEVD placement in our standard protocol for the management of PHH has proved to be a wise option for small patients.

Intrathecal Baclofen Therapy in a Child With Severe Scoliosis: Report of 2 Cases.

PubMed

Sasaki, Natsu; Ogiwara, Hideki

2016-08-01

Scoliosis is commonly found in children with cerebral palsy. Many patients with cerebral palsy and scoliosis undergo intrathecal baclofen (ITB) pump placement. The authors report 2 cases with cerebral palsy and severe scoliosis treated with intrathecal baclofen. The case of a 7-year-old boy with shunted hydrocephalus required surgical revision of the intrathecal catheter, while the other patient without shunt did not require revision. In the patient with shunted hydrocephalus, after the initial placement of baclofen pump and catheter at Th3 level, spasticity of lower extremities did not improve. The Indium(111) diethylenetriamine pentaacetic acid (In(111) DTPA) scintigraphy with injection of In(111) DTPA through the pump did not demonstrate distribution of the tracer to the lumbosacral area. Conversely, by direct injection of In(111) DTPA through lumbar puncture, the tracer distributed in the whole spinal canal. Replacement of the tip of the catheter caudal to the curve of the scoliosis improved the symptom. The authors suggest that, in patients with severe scoliosis and shunted hydrocephalus, it may be necessary to place the tip of the catheter caudal to the curve of the scoliosis for correction of spasticity of lower extremities. © 2016 International Neuromodulation Society.

Heterotaxy syndrome with severe pulmonary hypertension in an adult.

PubMed

Brandenburg, Vincent M; Krueger, Stefan; Haage, Patrick; Mertens, Peter; Riehl, Jochen

2002-05-01

Heterotaxy syndrome is a rare clinical entity in adults, characterized by situs ambiguus, congenital heart defects, and splenic malformations. We report the case of an adult with heterotaxy syndrome (including situs ambiguus, bilateral superior vena cava, hypoplastic right-sided spleen and portosystemic shunts) presenting with dyspnea due to severe pulmonary hypertension. Vasodilatory therapy was initiated, leading to marked reduction of clinical symptoms. This case exhibits 2 particular and partially novel features: primary diagnosis of heterotaxy syndrome may be delayed until adulthood, and heterotaxy syndrome may be associated with pulmonary hypertension, possibly on the basis of longstanding portosystemic shunts.

Following the canyon to reach and remove olfactory groove meningiomas.

PubMed

Stefini, Roberto; Zenga, Francesco; Giacomo, Esposito; Bolzoni, Andrea; Tartara, Fulvio; Spena, Giannantonio; Ambrosi, Claudia; Fontanella, Marco M

2017-04-01

Olfactory groove meningiomas (OGMs) represent approximately 10% of all intracranial meningiomas. They arise in the olfactory fossa, a variable depression delimited by the lateral lamella and perpendicular plate. The cribriform plate with the lateral lamella and ethmoidal and orbital roof could be viewed as a 'canyon' with the frontal sinus as the main entrance. Between January 2000 and December 2013, 32 consecutive patients underwent removal of OGMs through this 'canyon' at the Department of Neurosurgery of Brescia and Turin. Complete removal was achieved in all patients with this trans-frontal sinus subcranial approach (Simpson grade I; mean lesion volume, 46.6 cm3). Five patients (15.6%) experienced nasal CSF leakage, treated with external lumbar drain positioning for 4 days and resolved in all cases but one, which was re-operated. Two patients (6.2%) during the CSF leakage experienced meningitis at day 7 after surgery, both successfully treated by intravenous antibiotic therapy. After one month, one patient developed hydrocephalus, treated with a ventricular peritoneal shunt. In one patient, traction on the OGM caused bleeding of the callosomarginal artery, which was coagulated with superior frontal gyrus ischemia without neurological consequences. Glasgow Outcome Scale Score at 6 months was V in 29 patients, IV in one patient, and I in two patients. Advantages with this approach may include easy and early control of blood supply from its insertion in the skull base, minimal frontal lobe retraction, preservation of the frontal veins draining to the sagittal sinus, and a satisfactory aesthetic outcome.

Intracranial baroreflex yielding an early cushing response in human.

PubMed

Schmidt, E A; Czosnyka, Z; Momjian, S; Czosnyka, M; Bech, R A; Pickard, J D

2005-01-01

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

Outer brain barriers in rat and human development

PubMed Central

Brøchner, Christian B.; Holst, Camilla B.; Møllgård, Kjeld

2015-01-01

Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6–21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer. PMID:25852456

Outer brain barriers in rat and human development.

PubMed

Brøchner, Christian B; Holst, Camilla B; Møllgård, Kjeld

2015-01-01

Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer.

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

PubMed Central

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

General Anesthesia Inhibits the Activity of the “Glymphatic System”

PubMed Central

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; Martinez de Lizarrondo, Sara; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the “glymphatic system” hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent. PMID:29344300

General Anesthesia Inhibits the Activity of the "Glymphatic System".

PubMed

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; de Lizarrondo, Sara Martinez; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.

Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.

PubMed

Alvarado-Vazquez, P A; Morado-Urbina, C E; Castañeda-Corral, G; Acosta-Gonzalez, R I; Kitaura, H; Kimura, K; Takano-Yamamoto, T; Jiménez-Andrade, J M

2015-01-01

Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 μg/5 μL per joint), isotype control (rat IgG 10 μg/5 μL per joint) or PBS (5 μl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

PubMed

Rozen, Todd; Swidan, Sahar Z

2007-01-01

To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

Transcatheter Potts shunt creation in patients with severe pulmonary arterial hypertension: initial clinical experience.

PubMed

Esch, Jesse J; Shah, Pinak B; Cockrill, Barbara A; Farber, Harrison W; Landzberg, Michael J; Mehra, Mandeep R; Mullen, Mary P; Opotowsky, Alexander R; Waxman, Aaron B; Lock, James E; Marshall, Audrey C

2013-04-01

Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent-anchored by the vessel walls and surrounding tissue-serves as the shunt. TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Endoscopic third ventriculostomy (ETV) for idiopathic normal pressure hydrocephalus (iNPH).

PubMed

Tudor, Katarina Ivana; Tudor, Mario; McCleery, Jenny; Car, Josip

2015-07-29

Idiopathic normal pressure hydrocephalus (iNPH) is a type of communicating hydrocephalus also known as non-obstructive hydrocephalus. This type of hydrocephalus is caused by impaired cerebrospinal fluid reabsorption without any obstruction in the ventricular system and is associated with normal cerebrospinal fluid pressure. It is characterised clinically by gait disturbance, cognitive dysfunction, and urinary incontinence (known as the Hakim-Adams triad). The exact cause of iNPH is unknown. It may be managed conservatively or treated surgically by inserting a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt. However, a substantial number of patients do not respond well to surgical treatment, complication rates are high and there is often a need for further surgery. Endoscopic third ventriculostomy (ETV) is an alternative surgical intervention. It has been suggested that ETV may lead to better outcomes, including fewer complications. To determine the effectiveness of ETV for treatment of patients with iNPH compared to conservative therapy, or shunting of CSF using VP or VA shunts.To assess the perioperative and postoperative complication rates in patients with iNPH after ETV compared to conservative therapy, VP or VA shunting. We searched for eligible studies using ALOIS: a comprehensive register of dementia studies, The Cochrane Central Register of Controlled Trials (CENTRAL) and several bibliographic databases such as MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost) and LILACS (BIREME).We also searched the Database of Abstracts of Reviews of Effects (DARE) to identify potentially relevant reviews. The search strategy was adapted for other databases, using the most appropriate controlled vocabulary for each. We did not apply any language or time restrictions. The searches were performed in August 2014. We included randomised controlled trials (RCTs) of ETV treatment of iNPH. Patients had to have at least two symptoms of the Hakim-Adams triad. Exclusion criteria were obstructive causes of hydrocephalus, other significant intracranial pathology and other confirmed causes of dementia. The eligible comparators were conservative treatment or shunting using VP and VA shunts. Two review authors independently screened search results, selected eligible studies, assessed risk of bias and extracted data. We contacted trial authors for additional data. Only one study met the inclusion criteria: an RCT comparing effectiveness of ETV and non-programmable VP shunts in 42 patients with iNPH. The study was conducted in Brazil between 2009 and 2012. The overall study risk of bias was high. The primary outcome in the study was the proportion of patients with improved symptoms one year after surgery, determined as a change of at least two points on the Japanese NPH scale. Due to imprecision in the results, it was not possible to determine whether there was any difference between groups in the proportion of patients who improved 3 or 12 months after surgery (3 months: odds ration (OR) 1.12, 95% confidence interval (CI) 0.26 to 4.76, n = 42; 12 months: OR 2.5, 95% CI 0.62 to 10.11, n = 38). We were unable to estimate the effect of treatment on other efficacy outcomes (cognition, balance, function, gait and mobility) because they were inadequately reported. Of the 26 patients in the VP shunting group, 5 developed subdural hematoma postoperatively, while there were no complications among the 16 patients in the ETV group (OR 0.12, 95% CI 0.01 to 2.3, n = 42), but the estimate was too imprecise to determine whether this was likely to reflect a true difference in complication rates. This was also the case for rates of further surgical intervention (OR 1.4, 95% CI 0.31 to 6.24, n = 42). There were no deaths during the trial. We judged the quality of evidence for all outcomes to be very low because of a high risk of selection, attrition and reporting bias and serious imprecision in the results. The only randomised trial of ETV for iNPH compares it to an intervention which is not a standard practice (VP shunting using a non-programmable valve). The evidence from this study is inconclusive and of very low quality. Clinicians should be aware of the limitations of the evidence. There is a need for more robust research on this topic to be able to determine the effectiveness of ETV in patients with iNPH.

Use of programmable versus nonprogrammable shunts in the management of hydrocephalus secondary to aneurysmal subarachnoid hemorrhage: a retrospective study with cost-benefit analysis.

PubMed

Lee, Lester; King, Nicolas K K; Kumar, Dinesh; Ng, Yew Poh; Rao, Jai; Ng, Huiyu; Lee, Kah Keow; Wang, Ernest; Ng, Ivan

2014-10-01

The choice of programmable or nonprogrammable shunts for the management of hydrocephalus after aneurysmal subarachnoid hemorrhage (SAH) remains undefined. Variable intracranial pressures make optimal management difficult. Programmable shunts have been shown to reduce problems with drainage, but at 3 times the cost of nonprogrammable shunts. All patients who underwent insertion of a ventriculoperitoneal shunt for hydrocephalus after aneurysmal SAH between 2006 and 2012 were included. Patients were divided into those in whom nonprogrammable shunts and those in whom programmable shunts were inserted. The rates of shunt revisions, the reasons for adjustments of shunt settings in patients with programmable devices, and the effectiveness of the adjustments were analyzed. A cost-benefit analysis was also conducted to determine if the overall cost for programmable shunts was more than for nonprogrammable shunts. Ninety-four patients underwent insertion of shunts for hydrocephalus secondary to SAH. In 37 of these patients, nonprogrammable shunts were inserted, whereas in 57 programmable shunts were inserted. Four (7%) of 57 patients with programmable devices underwent shunt revision, whereas 8 (21.6%) of 37 patients with nonprogrammable shunts underwent shunt revision (p = 0.0413), and 4 of these patients had programmable shunts inserted during shunt revision. In 33 of 57 patients with programmable shunts, adjustments were made. The adjustments were for a trial of functional improvement (n = 21), overdrainage (n = 5), underdrainage (n = 6), or overly sunken skull defect (n = 1). Of these 33 patients, 24 showed neurological improvements (p = 0.012). Cost-benefit analysis showed $646.60 savings (US dollars) per patient if programmable shunts were used, because the cost of shunt revision is a lot higher than the cost of the shunt. The rate of shunt revision is lower in patients with programmable devices, and these are therefore more cost-effective. In addition, the shunt adjustments made for patients with programmable devices also resulted in better neurological outcomes.

TNF and granulocyte macrophage-colony stimulating factor interdependence mediates inflammation via CCL17

PubMed Central

Cook, Andrew D.; Khiew, Hsu-Wei; Christensen, Anne D.; Fleetwood, Andrew J.; Lacey, Derek C.; Smith, Julia E.; Förster, Irmgard

2018-01-01

TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity and both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory factor 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages in vitro and important for inflammatory pain, as well as for arthritic pain and disease. Here we provide evidence for a nexus between TNF and this pathway, and for TNF and GM-CSF interdependency. We report that the initiation of zymosan-induced inflammatory pain and zymosan-induced arthritic pain and disease are TNF dependent. Once arthritic pain and disease are established, blockade of GM-CSF or CCL17, but not of TNF, is still able to ameliorate them. TNF is required for GM-CSF–driven inflammatory pain and for initiation of GM-CSF–driven arthritic pain and disease, but not once they are established. TNF-driven inflammatory pain and TNF-driven arthritic pain and disease are dependent on GM-CSF and mechanistically require the same downstream pathway involving GM-CSF→CCL17 formation via JMJD3-regulated IRF4 production, indicating that GM-CSF and CCL17 can mediate some of the proinflammatory and algesic actions of TNF. Given we found that TNF appears important only early in arthritic pain and disease progression, targeting a downstream mediator, such as CCL17, which appears to act throughout the course of disease, could be effective at ameliorating chronic inflammatory conditions where TNF is implicated. PMID:29563337

Bioactivity of Autologous Irradiated Renal Cell Carcinoma Vaccines Generated by ex Vivo Granulocyte-Macrophage Colony-stimulating Factor Gene Transfer1

PubMed Central

Simons, Jonathan W.; Jaffee, Elizabeth M.; Weber, Christine E.; Levitsky, Hyam I.; Nelson, William G.; Carducci, Michael A.; Lazenby, Audrey J.; Cohen, Lawrence K.; Finn, Christy C.; Clift, Shirley M.; Hauda, Karen M.; Beck, Lisa A.; Leiferman, Kristen M.; Owens, Albert H.; Piantadosi, Steven; Dranoff, Glenn; Mulligan, Richard C.; Pardoll, Drew M.; Marshall, Fray F.

2014-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced, irradiated tumor vaccines induce potent, T-cell-mediated antitumor immune responses in preclinical models. We report the initial results of a Phase I trial evaluating this strategy for safety and the induction of immune responses in patients with metastatic renal cell carcinoma (RCC). Patients were treated in a randomized, double-blind dose-escalation study with equivalent doses of autologous, irradiated RCC vaccine cells with or without ex vivo human GM-CSF gene transfer. The replication-defective retroviral vector MFG was used for GM-CSF gene transfer. No dose-limiting toxicities were encountered in 16 fully evaluable patients. GM-CSF gene-transduced vaccines were equivalent in toxicity to nontransduced vaccines up to the feasible limits of autologous tumor vaccine yield. No evidence of autoimmune disease was observed. Biopsies of intradermal sites of injection with GM-CSF gene-transduced vaccines contained distinctive macrophage, dendritic cell, eosinophil, neutrophil, and T-cell infiltrates similar to those observed in preclinical models of efficacy. Histological analysis of delayed-type hypersensitivity responses in patients vaccinated with GM-CSF-transduced vaccines demonstrated an intense eosinophil infiltrate that was not observed in patients who received nontransduced vaccines. An objective partial response was observed in a patient treated with GM-CSF gene-transduced vaccine who displayed the largest delayed-type hypersensitivity conversion. No replication-competent retrovirus was detected in vaccinated patients. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous GM-CSF gene-transduced tumor vaccine for RCC patients. PMID:9108457

Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission.

PubMed

Adachi, Kristina; Song, Sophie X; Kao, Roy L; Van Dyne, Elizabeth; Kempert, Pamela; Deville, Jaime G

2016-08-01

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.

Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

PubMed Central

Kang, Ju-Hee; Irwin, David J.; Chen-Plotkin, Alice S.; Siderowf, Andrew; Caspell, Chelsea; Coffey, Christopher S.; Waligórska, Teresa; Taylor, Peggy; Pan, Sarah; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Simuni, Tanya; Tanner, Caroline M.; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Mollenhauer, Brit; Trojanowski, John Q.; Shaw, Leslie M.

2014-01-01

Importance We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1–42 (Aβ1–42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. Objective To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1–42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study. Design, Setting, and Participants Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. Main Outcomes and Measures The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1–42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. Results Slightly, but significantly, lower levels of Aβ1–42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1–42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1–42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1–42 and P-tau181 concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. Conclusions and Relevance In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1–42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression. PMID:23979011

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

PubMed

Patton, J H; Lyden, S P; Ragsdale, D N; Croce, M A; Fabian, T C; Proctor, K G

1998-05-01

Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Acute radiation syndrome (ARS) - treatment of the reduced host defense.

PubMed

Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

2012-01-01

The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250-400 μg GM-CSF/m(2) or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.

Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with defibrotide and recombinant human granulocyte colony-stimulating factor.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Longoni, Paolo; Milani, Raffaella; Milanesi, Marco; Guidetti, Anna; Haanstra, Krista; Jonker, Margaret; Cleris, Loredana; Magni, Michele; Formelli, Franca; Gianni, Alesssandro M

2004-01-01

The aim of this study was to evaluate the capacity of defibrotide in enhancing cytokine-induced hematopoietic mobilization in rhesus monkeys. Animals received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 100 microg/kg/day SC for 5 days) and, after a 4- to 6-week washout period, were remobilized with defibrotide (15 mg/kg/hour continuous intravenous for 5 days) plus rhG-CSF. Hematopoietic mobilization was evaluated by complete blood counts, differential counts, as well as frequency and absolute numbers of colony-forming cells (CFCs), high-proliferative potential CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). Compared to baseline values, rhG-CSF increased circulating CFCs, HPP-CFCs, and LTC-ICs by 158-, 125-, and 67-fold, respectively; the same figures for defibrotide/rhG-CSF were 299-, 1452-, and 295-fold, respectively. Defibrotide/rhG-CSF treatment compared to rhG-CSF alone increased CFCs, HPP-CFCs, and LTC-ICs by 1.4- (35,089 vs 25,825, p< or =0.02), 6- (4358 vs 748, p< or =0.02), and 5-fold (884 vs 168, p< or =0.04), respectively. We then evaluated the effects of a 2-day defibrotide treatment associated with a 5-day rhG-CSF treatment. Compared to rhG-CSF, defibrotide/rhG-CSF increased the mobilization of CFCs, HPP-CFCs, and LTC-ICs by 2- (31,128 vs 15,527, p< or =0.05), 8- (5361 vs 660, p< or =0.01), and 8-fold (954 vs 119, p< or =0.01), respectively. Our data demonstrate that in nonhuman primates: 1) defibrotide enhances rhG-CSF-elicited mobilization of primitive and committed progenitors; and 2) a 2-day defibrotide injection is as effective as a 5-day injection.

Management of cerebrospinal fluid leakage after anterior decompression for ossification of posterior longitudinal ligament in the thoracic spine: the utilization of a volume-controlled pseudomeningocele.

PubMed

Cho, Ji Young; Chan, Chee Keong; Lee, Sang-Ho; Choi, Won-Chul; Maeng, Dae Hyeon; Lee, Ho-Yeon

2012-06-01

Retrospective review To determine the efficacy of management of cerebrospinal fluid (CSF) leakage after the anterior thoracic approach. CSF leakage after incidental durotomy commonly occurs after anterior thoracic ossification of posterior longitudinal ligament (OPLL) surgery. Pseudomeningocele will invariably form under such circumstances. Among them, uncontrolled CSF leakage with a fistulous condition is problematic. As a solution, we have managed these durotomies with chest drains alone without any CSF drainage by the concept of a "volume-controlled pseudomeningocele." Between 2001 and 2009, CSF leakage occurred in 26 patients (37.7%) of the total 69 patients who underwent anterior decompression for thoracic OPLL. In the initial 11 cases, subarachnoid drainage was utilized as an augmentive measure in combination with chest tube drainage in the postoperative period (group A). In the subsequent 15 cases, the durotomy was managed in a similar manner but in the absence of any subarachnoid drainage (group B). Various parameters such as the duration of postoperative hospital stay, clinical outcome score, drainage output, resolution of CSF leakage, complications, and additional surgery performed were analyzed and compared between the 2 groups. A resolution of the CSF leakage grading system was also proposed for the residual pseudomeningocele that formed in each group. There were statistically no significant differences in the outcome parameters between the 2 groups and also in patients with grade I or grade II residual pseudomeningocele of the new grading system. Two complications occurred in group A. No reexploration for persistent CSF leakage was required in both groups. CSF leakage managed with controlled chest tube drainage can produce a comparable result with those with additional subarachnoid drainage when watertight dural repair is impossible. The concept of controlled pseudomeningocele may be a useful and practical technique for the treatment of CSF leakage after anterior thoracic OPLL surgery.

Using CSF biomarkers to replicate genetic associations in Alzheimer's disease.

PubMed

Schott, Jonathan M

2012-07-01

Defining cases and controls on the basis of biomarkers rather than clinical diagnosis may reduce sample sizes required for genetic studies. The aim of this study was to assess whether characterizing case/control status on the basis of cerebrospinal fluid (CSF) profile would increase power to replicate known genetic associations for Alzheimer's disease (AD). Independent of clinical diagnosis, Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects with 2 CSF biomarkers for AD (Aβ1-42 < 192 pg/mL and tau phosphorylated at threonine 181 (p-tau) > 23 pg/mL, "CSF-positive") were compared with those without CSF evidence for AD (Aβ1-42 > 192 pg/mL and 181-phosphorylated tau < 23 pg/mL, "CSF-negative"). Minor allele frequency (MAF) and odds ratios (ORs) between these 2 groups were calculated for 7 single-nucleotide polymorphisms (SNPs) of interest. Two hundred thirty-two individuals were CSF-positive and 94 CSF-negative. There were no differences in age (74.7 ± 7.2 vs. 75.0 ± 6.5 years, p = 0.7), but significant differences in Mini Mental State Examination (MMSE) (25.9 ± 2.6 vs. 28.2 ± 1.7, p < 0.001) between the CSF-positive and CSF-negative groups. Significant differences in MAF (p < 0.05, uncorrected) were seen for CR1 (rs1408077; OR, 1.59; 95% confidence interval [CI], 1.01-2.49), PICALM (rs541458; OR, 0.68, 95% CI, 0.47-0.98), TOMM40 (rs2075650; OR, 4.30; 95% CI, 2.61-7.06); and possession of 1 or more APOE ε4 alleles (OR, 9.84; 95% CI, 5.48-17.67). These results suggest that using biomarkers of AD pathology to define case and control status may increase power in genetic association studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Leukemic meningitis in a patient with hairy cell leukemia. A case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

1984-09-15

Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.

Congenital portosystemic shunts with and without gastrointestinal bleeding - case series.

PubMed

Gong, Ying; Zhu, Hui; Chen, Jun; Chen, Qi; Ji, Min; Pa, Mier; Zheng, Shan; Qiao, Zhongwei

2015-12-01

The clinical presentation of congenital portosystemic shunt is variable and gastrointestinal bleeding is an uncommon presentation. To describe the imaging features of congenital portosystemic shunt as it presented in 11 children with (n = 6) and without gastrointestinal bleeding (n = 5). We performed a retrospective study on a clinical and imaging dataset of 11 children diagnosed with congenital portosystemic shunt. A total of 11 children with congenital portosystemic shunt were included in this study, 7 with extrahepatic portosystemic shunts and 4 with intrahepatic portosystemic shunts. Six patients with gastrointestinal bleeding had an extrahepatic portosystemic shunt, and the imaging results showed that the shunts originated from the splenomesenteric junction (n = 5) or splenic vein (n = 1) and connected to the internal iliac vein. Among the five cases of congenital portosystemic shunt without gastrointestinal bleeding, one case was an extrahepatic portosystemic shunt and the other four were intrahepatic portosystemic shunts. Most congenital portosystemic shunt patients with gastrointestinal bleeding had a shunt that drained portal blood into the iliac vein via an inferior mesenteric vein. This type of shunt was uncommon, but the concomitant rate of gastrointestinal bleeding with this type of shunt was high.

Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia

PubMed Central

Hustinx, W N M; Van Kessel, C P M; Heezius, E; Burgers, S; Lammers, J-W; Hoepelman, I M

1998-01-01

Considerable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe infections in non-neutropenic hosts. This beneficial effect is attributed to an enhancement of granulopoiesis and neutrophil function, the latter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. We compared neutrophil function and phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator-dependent pneumonia, at baseline and following initiation of G-CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatment compared with baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml. After correction for lavage dilution effects, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (FcγRI, FcγRII, FcγRIII, CR3, and l-selectin) or indicators of neutrophil function such as respiratory burst activity, phagocytosis and killing of Candida albicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortality of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression. PMID:9649199

Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection

PubMed Central

Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2016-01-01

Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = –0.41, p < 0.001) and folate (r = –0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals. PMID:27441551

Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.

PubMed

Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2016-01-01

To investigate the role of homocysteine in neuronal injury in HIV infection. Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

PubMed

Yoshida, M; Karasawa, M; Naruse, T; Fukuda, M; Hirashima, K; Oh, H; Ninomiya, H; Abe, T; Saito, K; Shishido, H; Moriyama, Y; Shibata, A; Motoyoshi, K; Nagata, N; Miura, Y

1999-02-01

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

PubMed

Fardo, David W; Katsumata, Yuriko; Kauwe, John S K; Deming, Yuetiva; Harari, Oscar; Cruchaga, Carlos; Nelson, Peter T

2017-04-01

Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes. The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p<0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10 -5 ). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages.

PubMed

Jin, Xueting; Kruth, Howard S

2016-06-30

A protocol is presented for cell culture of macrophage colony-stimulating factor (M-CSF) differentiated human monocyte-derived macrophages. For initiation of experiments, fresh or frozen monocytes are cultured in flasks for 1 week with M-CSF to induce their differentiation into macrophages. Then, the macrophages can be harvested and seeded into culture wells at required cell densities for carrying out experiments. The use of defined numbers of macrophages rather than defined numbers of monocytes to initiate macrophage cultures for experiments yields macrophage cultures in which the desired cell density can be more consistently attained. Use of cryopreserved monocytes reduces dependency on donor availability and produces more homogeneous macrophage cultures.

Use of the Viatorr Expanded Polytetrafluoroethylene-Covered Stent-Graft for Transjugular Intrahepatic Portosystemic Shunt Creation in Children: Initial Clinical Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mermuys, Koen; Maleux, Geert, E-mail: geert.maleux@uzleuven.be; Heye, Sam

2008-07-15

Four children, three boys and one girl, with a median age of 9 years 8 months, underwent transjugular intrahepatic portosystemic shunt creation with an expanded polytetrafluoroethylene (e-PTFE)-covered nitinol stent. The stent-graft was successfully placed in all four patients without any complication. Clinical and biochemical improvement was noted in all four patients during follow-up. Radiological follow-up with use of duplex ultrasound showed a recurrent stenosis of the shunt 180 days after stent-graft implantation in one patient. This was treated with placement of an additional stent-graft, re-expanding completely the recurrent stenosis. In the other three patients, the stent-graft remained fully patent untilmore » the end of the study or until orthotopic liver transplantation. These preliminary results suggest that use of the Viatorr ePTFE-covered stent-graft in children is safe and feasible, with potentially the same high patency rate and improved clinical outcome as reported in adult patients.« less

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

Granulocyte colony-stimulating factor in toxic epidermal necrolysis (TEN) and Chelsea & Westminster TEN management protocol [corrected].

PubMed

de Sica-Chapman, A; Williams, G; Soni, N; Bunker, C B

2010-04-01

Toxic epidermal necrolysis (TEN) is a rare but life-threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. We observed that in two cases of severe TEN, dramatic re-epithelialization and recovery coincided with the introduction of granulocyte colony-stimulating factor (G-CSF) for neutropenia. We explain how addition of the G-CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re-epithelialization. G-CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G-CSF should be considered in treating severe TEN irrespective of the severity of neutropenia.

Single-Photon Emission Computed Tomography Is an Ambiguous Imaging Method on Initial Diagnosis for Acute Encephalopathy.

PubMed

Yamanaka, Gaku; Morishita, Nastumi; Oana, Shingo; Takeshita, Mika; Morichi, Shinichiro; Ishida, Yu; Kashiwagi, Yasuyo; Kawashima, Hisashi

2016-01-01

The distinction between acute encephalopathy (AE) and convulsive disorders with pyrexia may be problematic. We analyzed the clinical and laboratory features in 127 children who were admitted for suspected AE. They were categorized into (1) definite acute encephalopathy group (DAEG; n = 17, abnormal findings on electroencephalography [EEG], magnetic resonance imaging, or single-photon emission computed tomography [SPECT] with prolonged impaired consciousness), (2) probable acute encephalopathy group (PAEG; n = 21, abnormal findings without prolonged impaired consciousness), and (3) nonacute encephalopathy group (NAEG; n = 89). Cerebrospinal fluid interleukin-6 (CSF IL-6), and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase levels were significantly higher in DAEG compared with NAEG but not PAEG. No significant differences were observed between DAEG and PAEG except for serum creatinine levels. In PAEG, an area of hypoperfusion was observed on SPECT images of nine patients with normal CSF IL-6 levels. AE was suspected in two PAEG patients who exhibited high CSF IL-6 levels and abnormal EEG findings without abnormal SPECT findings. All seven patients with severe neurological sequelae were categorized to DAEG. CSF IL-6 and serum AST, ALT, and creatine kinase levels may be valid predictors of typical AE; prolonged impaired consciousness is an important sign of AE. However, SPECT may not be suitable for initial diagnosis of AE. Georg Thieme Verlag KG Stuttgart · New York.

Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy.

PubMed

Cosler, Leon E; Sivasubramaniam, Visaharan; Agboola, Olayemi; Crawford, Jeffrey; Dale, David; Lyman, Gary H

2005-01-01

Febrile neutropenia (FN) in patients with cancer treated with chemotherapy has traditionally been managed with inpatient broad-spectrum antibiotics until the infection and neutropenia have resolved. A newer strategy is outpatient oral or intravenous antibiotics in selected patients after an initial hospitalization. We sought to determine these costs, both overall and relative to those of traditional management, and the optimal role of prophylactic colony-stimulating factor (CSF) in patients at greatest risk for FN. Existing economic decision models were modified by incorporating a treatment strategy for FN in which patients are classified as high- and low-risk according to criteria described by Talcott. Low-risk patients were assumed to be treated as outpatients. Overall costs with the revised economic model were assessed and sensitivity analyses were performed. The costs of an episode of FN were estimated as 1) no CSF: dollar 13,355; 2) CSF with hospitalization for FN: dollar 8677; and 3) CSF with risk stratification and outpatient management in low-risk patients: dollar 8188. The risk threshold for the cost-effective use of CSF was only slightly lower with outpatient treatment. When all patients with FN are treated as inpatients and the cost of hospitalization is dollar 1750/day the risk threshold for FN at which prophylactic CSF becomes cost-effective is 16%. It is 15% when low-risk patients are treated as outpatients. Outpatient treatment slightly decreases the risk threshold for FN at which prophylactic CSF becomes cost-effective. The limited economic effect of this strategy may be because the patients who were at greatest risk of complications had significantly longer lengths of stay and accounted for most of the hospitalization costs.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort.

PubMed

Kim, S; Swaminathan, S; Shen, L; Risacher, S L; Nho, K; Foroud, T; Shaw, L M; Trojanowski, J Q; Potkin, S G; Huentelman, M J; Craig, D W; DeChairo, B M; Aisen, P S; Petersen, R C; Weiner, M W; Saykin, A J

2011-01-04

CSF levels of Aβ1-42, t-tau, and p-tau181p are potential early diagnostic markers for probable Alzheimer disease (AD). The influence of genetic variation on these markers has been investigated for candidate genes but not on a genome-wide basis. We report a genome-wide association study (GWAS) of CSF biomarkers (Aβ1-42, t-tau, p-tau181p, p-tau181p/Aβ1-42, and t-tau/Aβ1-42). A total of 374 non-Hispanic Caucasian participants in the Alzheimer's Disease Neuroimaging Initiative cohort with quality-controlled CSF and genotype data were included in this analysis. The main effect of single nucleotide polymorphisms (SNPs) under an additive genetic model was assessed on each of 5 CSF biomarkers. The p values of all SNPs for each CSF biomarker were adjusted for multiple comparisons by the Bonferroni method. We focused on SNPs with corrected p<0.01 (uncorrected p<3.10×10(-8)) and secondarily examined SNPs with uncorrected p values less than 10(-5) to identify potential candidates. Four SNPs in the regions of the APOE, LOC100129500, TOMM40, and EPC2 genes reached genome-wide significance for associations with one or more CSF biomarkers. SNPs in CCDC134, ABCG2, SREBF2, and NFATC4, although not reaching genome-wide significance, were identified as potential candidates. In addition to known candidate genes, APOE, TOMM40, and one hypothetical gene LOC100129500 partially overlapping APOE; one novel gene, EPC2, and several other interesting genes were associated with CSF biomarkers that are related to AD. These findings, especially the new EPC2 results, require replication in independent cohorts.

[Mesenteric-cava shunt's results with autologous jugular vein graft in children with pre-sinusoidal portal hypertension].

PubMed

Leal, N; López Santamaría, M; Gámez, M; Murcia, J; Andolfi, G; Berrocal, T; Frauca, E; Jara, P; Tovar, J

2002-07-01

Presinusoidal portal hypertension (PPH) in children evaluates without functional hepatic damage, and with the time, trends to compensate through the creation of spontaneous portosystemic shunts. Nevertheless, some patients suffer episodes of gastrointestinal bleeding (GIB) that because of its frequency or severity, force to propose the change of surgical treatment. To evaluate the results of the mesocaval shunt (MCS) with autologous jugular vein in children with PPH. Among the 32 children with PPH treated in our Hospital in the last 7 years, 10 had episodes of GIB that forced to perform a surgical shunt. The types of shunt were distal splenorenal in 3 patients and mesocaval in 7. These 7 cases are the material of this study. The origin of the PPH was a cavernomatosis transformation of the portal vein in 6 cases and a congenital hepatic fibrosis in 1. Before the surgery the average number of episodes of GIB was 9 (range 2-15); all the patients needed transfusion of blood products and variceal sclerosis. In 2 cases a tamponade with the Sengtaken balloon was required and 5 patients were treated with somatostatin and propranolol. The Doppler ultrasounds revealed and intense hepatofugal collateral circulation in all the cases. The initial flow through the shunt was adequate in all the patients except one who required a percutaneous balloon dilatation. Only this patient has suffered an episode of GIB. The hyperesplenism signs disappeared or improved in all the seven cases and the collateral circulation was significantly reduced. The pressure in the splenic territory decreased around 50% in the 4 patients that was measured. There were no cases of encephalopasty and only one child with congenital hepatic fibrosis shows signs of mild hepatic disfunction. The medium follow up post-shunt is 32 months (range 8 m-6 years). The MCS prevents the GIB in the PPH not responsive to the conservative treatment; its effectiveness is related with an adequate permeability though the graft and at least in the cases with portal cavernomatosis (the most frequent in children) doesn't produce hepatic dysfunction. Doppler ultrasounds give a very precise information about the post-surgical situation and are an excellent method of follow up.

Vascular Plug Assisted Retrograde Transvenous Obliteration (PARTO) for Gastric Varix Bleeding Patients in the Emergent Clinical Setting

PubMed Central

Yang, Heechul; Lee, Chun Kyon; Kim, Gun Bea

2016-01-01

Purpose To evaluate the technical feasibility and safety of vascular plug assisted retrograde transvenous obliteration (PARTO) for bleeding gastric varix performed in the emergent clinical setting and describe the mid-term clinical results. Materials and Methods From April 2012 to January 2015, emergent PARTO was tried in total 9 patients presented with active gastric varix bleeding. After initial insufficient or failure of endoscopic approach, they underwent PARTO in the emergent clinical setting. Gelatin sponge embolization of both gastrorenal (GR) shunt and gastric varix was performed after retrograde transvenous placement of a vascular plug in GR shunt. Coil assisted RTO (CARTO) was performed in one patient who had challenging GR shunt anatomy for vascular plug placement. Additional embolic materials, such as microcoils and NBCA glue-lipiodol mixture, were required in three patients to enhance complete occlusion of GR shunt or obliteration of competitive collateral vessels. Clinical success was defined as no variceal rebleeding and disappearance of gastric varix. Results All technical and clinical success–i.e., complete GR shunt occlusion and offending gastric varix embolization with immediate bleeding control–was achieved in all 9 patients. There was no procedure-related complication. All cases showed successful clinical outcome during mean follow up of 17 months (12–32 months), evidenced by imaging studies, endoscopy and clinical data. In 4 patients, mild worsening of esophageal varices or transient ascites was noted as portal hypertensive related change. Conclusion Emergent PARTO is technically feasible and safe, with acceptable mid-term clinical results, in treating active gastric varix bleeding. PMID:27189294

Case report: imaging and treatment of ophthalmic manifestations in oculodentodigital dysplasia.

PubMed

Mosaed, Sameh; Jacobsen, Bradley H; Lin, Ken Young

2016-01-07

Diagnostic and surgical management of severe chronic angle- closure glaucoma secondary to ciliary body cysts can be difficult to manage in a patient with oculodentodigital dysplasia. A 6-year old girl with oculodentodigital dysplasia, with progressive chronic angle- closure glaucoma secondary to ciliary body cysts presented to our clinic. The initial examination revealed counting fingers vision in the left eye. Intraocular pressure (IOP), as assessed by tonopen, was 31 mm Hg. Ultrasound biomicroscopy revealed ciliary body cysts in the left eye, and gonioscopy confirmed chronic angle closure. A tube shunt was placed to control the elevated IOP. A year after her tube shunt placement in the left eye, ultrasound biomiscropy was performed on her right eye and showed no ciliary body cysts. Gonioscopy in the right eye revealed an open angle to the ciliary body band. Subsequent serial gonioscopy every 3 months showed gradual narrowing of the right eye angle and finally three-and-a-half years after tube placement of the left eye, her right eye IOP became uncontrolled with medications alone and a tube shunt was similarly placed in the right eye. Intraoperative ultrasound biomicroscopy performed at the time of the right eye tube shunt revealed extensive ciliary body cysts in the right eye. Her IOP in both eyes have been well controlled since the placement of tube shunts. This is one of the first reported cases of severe chronic angle- closure glaucoma secondary to ciliary body cysts in a patient with oculodentodigital dysplasia. We believe that early screening for ciliary body cysts is important in patients with oculodentodigital dysplasia.

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

PubMed Central

Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure. PMID:29713348

Predicting Behavioral Problems in Craniopharyngioma Survivors after Conformal Radiation Therapy

PubMed Central

Dolson, Eugenia P.; Conklin, Heather M.; Li, Chenghong; Xiong, Xiaoping; Merchant, Thomas E.

2009-01-01

Background Although radiation therapy is a primary treatment for craniopharyngioma, it can exacerbate existing problems related to the tumor and pre-irradiation management. Survival is often marked by neurologic deficits, panhypopituitarism, diabetes insipidus, cognitive deficiencies and behavioral and social problems. Procedure The Achenbach Child Behavior Checklist (CBCL) was used to evaluate behavioral and social problems during the first five years of follow-up in 27 patients with craniopharyngioma treated with conformal radiation therapy. Results All group averages for the CBCL scales were within the age-typical range at pre-irradiation baseline. Extent of surgical resection was implicated in baseline differences for the Internalizing, Externalizing, Behavior Problem and Social scores. Significant longitudinal changes were found in Internalizing, Externalizing, Behavior Problem and School scores that correlated with tumor and treatment related factors. Conclusions The most common variables implicated in post-irradiation behavioral and social problems were CSF shunting, presence of an Ommaya reservoir, diabetes insipidus, and low pre-irradiation growth hormone levels. PMID:19191345

Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria.

PubMed

Fijen, C A; Kuijper, E J; Tjia, H G; Daha, M R; Dankert, J

1994-05-01

Nongroupable meningococci or bacteria related to the genus Neisseria rarely cause meningitis. Complement deficiency has been identified as a major predisposing factor for meningococcal disease. To assess whether patients with meningitis due to such strains have a complement deficiency, we studied 12 persons. Six patients had meningitis due to nongroupable strains of meningococci, and six patients had meningitis due to Moraxella species or Acinetobacter species. Inherited complement component C7 or C8 deficiency was found in two persons who had had meningitis due to nongroupable meningococci, and one C8-deficient person had had meningitis caused by Moraxella osloensis. Hypocomplementemia resulting from CSF drain-associated shunt nephritis was found in one person with meningitis due to Moraxella nonliquefaciens and in one person with meningitis due to Acinetobacter lwoffi. This rather high frequency of inherited or acquired complement deficiencies among patients with meningitis due to nongroupable meningococci, Moraxella species, and Acinetobacter species justifies the recommendation that such patients must be studied for complement deficiency.

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach.

PubMed

Dobran, Mauro; Nasi, Davide; Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

CPA melanoma: diagnosis and management.

PubMed

Brackmann, Derald E; Doherty, Joni K

2007-06-01

Melanoma rarely invades the cerebellopontine angle (CPA) and can evade accurate diagnosis, which may alter management decisions. Diagnosis may be facilitated via careful history, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) analysis. Retrospective case review. Tertiary referral center. Thirteen internal auditory canal/CPA lesions in eight patients who presented with CPA syndrome and who had a pathological diagnosis consistent with malignant melanoma. There were four bilateral and four unilateral lesions. Six of eight patients had a history of melanoma. One was apparently primary CPA lesion, whereas all others were metastatic. T1- and T2-weighted precontrast and postcontrast gadolinium-enhanced MRI were obtained, including fat suppression and fluid-attenuated inversion recovery sequence images in two patients; lumbar puncture with CSF centrifugation and cytological analysis confirmed the diagnosis in two patients. Translabyrinthine craniotomy was performed for tumor extirpation in five patients. Symptoms at presentation, MRI findings, presence of malignant cells in CSF, tumor progression, intraoperative findings, response to treatment, time interval from initial diagnosis of melanoma elsewhere, and survival. Seven of eight patients had history and/or MRI findings suggestive of malignancy in the internal auditory canal and/or CPA, and diagnosis was confirmed via CSF analysis in two patients. In one patient, diagnosis was made at surgery. Internal auditory canal melanoma portends a grim prognosis, can occur up to 17 years after initial melanoma diagnosis/treatment, and can be detected with appropriate MRI sequences, especially enhanced fluid-attenuated inversion recovery images. In disseminated cases, diagnosis can be confirmed with lumbar puncture demonstrating malignant cells. Management includes tumor resection when melanoma seems to be solitary and malignant cells are not present in CSF. Intrathecal chemotherapy and radiation are recommended for dissemination, although the survival rate is still poor.

A sequential erythropoietin and GM-CSF schedule offers clinical benefits in the treatment of anaemia in myelodysplastic syndromes.

PubMed

Bernell, P; Stenke, L; Wallvik, J; Hippe, E; Hast, R

1996-08-01

In order to reduce anaemia in patients with myelodysplastic syndromes (MDS) a stepwise treatment protocol including erythropoietin (EP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was designed. Thirty-seven MDS patients (stages I-III) with symptomatic anaemia were first given EPO 10,000 U s.c. 3 times weekly for 6 weeks. Those not responding, i.e. increased their haemoglobin levels > 15 g/l, proceeded into the second phase of the study where GM-CSF (200 micrograms/d. s.c. on weeks 1-6) was combined with EPO (10,000 U s.c. 3 times weekly on weeks 5-14). Following the initial EPO treatment phase, 14 of the 37 patients (38%) responded with increased haemoglobin levels. Responders were significantly different from non-responders in that their pre-treatment values of s-EPO, s-LDH and bone marrow blast cell counts were lower, their baseline haemoglobin levels higher and their transfusion dependency less pronounced. Eighteen of the 23 non-responders proceeded into the second phase, 13 of those were evaluable having completed the entire schedule. Three of the 13 initially EPO resistant patients (23%) responded to the GM-CSF/EPO combination with increased haemoglobin levels, suggesting a positive synergy between the two cytokines. Thus, the overall response rate to the present protocol was 46% (17 of 37 cases), but only a limited subset of the patients did clearly benefit from the combined GM-CSF/EPO administration. Therefore, we believe this step-wise approach to multiple growth factor treatment in MDS, starting with EPO alone and reserving the combination for refractory cases, has considerable advantages, taking into account both medical and socio-economical aspects.

Diagnosis of Meningococcal Meningitis by Broad-Range Bacterial PCR with Cerebrospinal Fluid

PubMed Central

Kotilainen, Pirkko; Jalava, Jari; Meurman, Olli; Lehtonen, Olli-Pekka; Rintala, Esa; Seppälä, Olli-Pekka; Eerola, Erkki; Nikkari, Simo

1998-01-01

We used broad-range bacterial PCR combined with DNA sequencing to examine prospectively cerebrospinal fluid (CSF) samples from patients with suspected meningitis. Fifty-six CSF samples from 46 patients were studied during the year 1995. Genes coding for bacterial 16S and/or 23S rRNA genes could be amplified from the CSF samples from five patients with a clinical picture consistent with acute bacterial meningitis. For these patients, the sequenced PCR product shared 98.3 to 100% homology with the Neisseria meningitidis sequence. For one patient, the diagnosis was initially made by PCR alone. Of the remaining 51 CSF samples, for 50 (98.0%) samples the negative PCR findings were in accordance with the negative findings by bacterial culture and Gram staining, as well as with the eventual clinical diagnosis for the patient. However, the PCR test failed to detect the bacterial rRNA gene in one CSF sample, the culture of which yielded Listeria monocytogenes. These results invite new research efforts to be focused on the application of PCR with broad-range bacterial primers to improve the etiologic diagnosis of bacterial meningitis. In a clinical setting, Gram staining and bacterial culture still remain the cornerstones of diagnosis. PMID:9665992

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

PubMed

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

Validation of a commercially available enzyme-linked immunoabsorbent assay for the quantification of human α-Synuclein in cerebrospinal fluid.

PubMed

Kruse, Niels; Mollenhauer, Brit

2015-11-01

The quantification of α-Synuclein in cerebrospinal fluid (CSF) as a biomarker has gained tremendous interest in the last years. Several commercially available immunoassays are emerging. We here describe the full validation of one commercially available ELISA assay for the quantification of α-Synuclein in human CSF (Covance alpha-Synuclein ELISA kit). The study was conducted within the BIOMARKAPD project in the European initiative Joint Program for Neurodegenerative Diseases (JPND). We investigated the effect of several pre-analytical and analytical confounders: i.e. (1) need for centrifugation of freshly drawn CSF, (2) sample stability, (3) delay of freezing, (4) volume of storage aliquots, (5) freeze/thaw cycles, (6) thawing conditions, (7) dilution linearity, (8) parallelism, (9) spike recovery, and (10) precision. None of these confounders influenced the levels of α-Synuclein in CSF significantly. We found a very high intra-assay precision. The inter-assay precision was lower than expected due to different performances of kit lots used. Overall the validated immunoassay is useful for the quantification of α-Synuclein in human CSF. Copyright © 2015 Elsevier B.V. All rights reserved.

The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

PubMed Central

Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

2010-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

[Pleomorphic carcinoma of the lung with high serum granulocyte colony stimulating factor, suggested of pulmonary abscess by preoperative radiology; report of a case].

PubMed

Mizuno, Mikoto; Miyoshi, Tatsu; Nabeshima, Kazuki; Iwasaki, Akinori; Shirakusa, Takaho

2006-08-01

A 52-year-old man with a history of heavy smoking was hospitalized for evaluation of fever. Pulmonary abscess was initially suspected by computed tomography (CT) showing an ovoid, well-demarcated nodule of 61 mm in diameter with coarse calcification in S2a of the right lung. The patient was treated with antibiotics, but no improvement was seen in inflammatory reactions or lesion size. Marked leukocytosis and high level of granulocyte colony stimulating factor (G-CSF) was shown by laboratory examination. To improve patient condition and ensure correct diagnosis, right upper lobectomy of the lung was performed. Pleomorphic carcinoma of the lung was subsequently diagnosed. G-CSF producing tumor was suspected, since the normalization of serum G-CSF level followed by the improvement of both fever and inflammatory reaction was observed postoperatively. We also present herein a review of 22 Japanese cases of pleomorphic carcinoma producing G-CSF of the lung, characterized by leukocytosis.

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

PubMed

Ueda, T; Kawai, Y; Sugiyama, T; Takeuchi, N; Yoshida, A; Iwasaki, H; Wano, Y; Tsutani, H; Kamada, N; Nakamura, T

1993-12-01

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

Economic Analysis of Classical Swine Fever Surveillance in the Netherlands.

PubMed

Guo, X; Claassen, G D H; Oude Lansink, A G J M; Loeffen, W; Saatkamp, H W

2016-06-01

Classical swine fever (CSF) is a highly contagious pig disease that causes economic losses and impaired animal welfare. Improving the surveillance system for CSF can help to ensure early detection of the virus, thereby providing a better initial situation for controlling the disease. Economic analysis is required to compare the benefits of improved surveillance with the costs of implementing a more intensive system. This study presents a comprehensive economic analysis of CSF surveillance in the Netherlands, taking into account the specialized structure of Dutch pig production, differences in virulence of CSF strains and a complete list of possible surveillance activities. The starting point of the analysis is the current Dutch surveillance system (i.e. the default surveillance-setup scenario), including the surveillance activities 'daily clinical observation by the farmer', 'veterinarian inspection after a call', 'routine veterinarian inspection', 'pathology in AHS', 'PCR on tonsil in AHS', 'PCR on grouped animals in CVI' and 'confirmatory PCR by NVWA'. Alternative surveillance-setup scenarios were proposed by adding 'routine serology in slaughterhouses', 'routine serology on sow farms' and 'PCR on rendered animals'. The costs and benefits for applying the alternative surveillance-setup scenarios were evaluated by comparing the annual mitigated economic losses because of intensified CSF surveillance with the annual additional surveillance costs. The results of the cost-effectiveness analysis show that the alternative surveillance-setup scenarios with 'PCR on rendered animals' are effective for the moderately virulent CSF strain, whereas the scenarios with 'routine serology in slaughterhouses' or 'routine serology on sow farms' are effective for the low virulent strain. Moreover, the current CSF surveillance system in the Netherlands is cost-effective for both moderately virulent and low virulent CSF strains. The results of the cost-benefit analysis for the moderately virulent CSF strain indicate that the current surveillance system in the Netherlands is adequate. From an economic perspective, there is little to be gained from intensifying surveillance. © 2014 Blackwell Verlag GmbH.

T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

PubMed Central

Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

2016-01-01

An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an “inverse” configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF. PMID:26942913

T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

PubMed

Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

2016-01-01

An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF.

Colony-stimulating factor use and impact on febrile neutropenia among patients with newly diagnosed breast, colorectal, or non-small cell lung cancer who were receiving chemotherapy.

PubMed

McCune, Jeannine S; Sullivan, Sean D; Blough, David K; Clarke, Lauren; McDermott, Cara; Malin, Jennifer; Ramsey, Scott

2012-01-01

To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC). Retrospective claims analysis. The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records. A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy. Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia. The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes. © 2012 Pharmacotherapy Publications, Inc.

Outcomes of systemic to pulmonary artery shunts in patients weighing less than 3 kg: analysis of shunt type, size, and surgical approach.

PubMed

Myers, John W; Ghanayem, Nancy S; Cao, Yumei; Simpson, Pippa; Trapp, Katie; Mitchell, Michael E; Tweddell, James S; Woods, Ronald K

2014-02-01

To evaluate outcomes of systemic to pulmonary artery shunts (SPS) in patients weighing less than 3 kg with regard to shunt type, shunt size, and surgical approach. Patients weighing less than 3 kg who underwent modified Blalock-Taussig or central shunts with polytetrafluoroethylene grafts at our institution from January 1, 2000, to May 31, 2011, were reviewed. Patients who had undergone other major concomitant procedures were excluded from the analysis. Primary outcomes included mortality (discharge mortality and mortality before next planned palliative procedure or definitive repair), cardiac arrest and/or extracorporeal membrane oxygenation (ECMO), and shunt reintervention. In this cohort of 80 patients, discharge survival was 96% (77/80). Postoperative cardiac arrest or ECMO occurred in 6/80 (7.5%), and shunt reintervention was required in 14/80 (17%). On univariate analysis, shunt reintervention was more common in patients with 3-mm shunts (11/30, 37%) compared with 3.5-mm (2/36, 6%) or 4-mm shunts (1/14, 7%) (P < .003). There were no statistically significant associations between shunt type, shunt size, or surgical approach and cardiac arrest/ECMO or mortality. Multiple logistic regression demonstrated that a shunt size of 3 mm (P = .019) and extracardiac anomaly (P = .047) were associated with shunt reintervention, whereas no variable was associated with cardiac arrest/ECMO or mortality. In this high-risk group of neonates weighing less than 3 kg at the time of SPS, survival to discharge and the next planned surgical procedure was high. Outcomes were good with the 3.5- and 4-mm shunts; however, shunt reintervention was common with 3-mm shunts. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Characterization of Complications Associated with Open and Endoscopic Craniosynostosis Surgery at a Single Institution

PubMed Central

Han, Rowland H.; Nguyen, Dennis C.; Bruck, Brent S.; Skolnick, Gary B.; Yarbrough, Chester K.; Naidoo, Sybill D.; Patel, Kamlesh B.; Kane, Alex A.; Woo, Albert S.; Smyth, Matthew D.

2016-01-01

Object We present a retrospective cohort study examining complications in patients undergoing surgery for craniosynostosis using both minimally invasive endoscopic and open approaches. Methods Over the past ten years, 295 non-syndromic patients (140 endoscopic, 155 open) and 33 syndromic patients (10 endoscopic, 23 open) met our criteria. Variables analyzed included: age at surgery, presence of pre-existing CSF shunt, skin incision method, estimated blood loss (EBL), transfusions of packed red blood cells (PRBC), use of intravenous (IV) steroids or tranexamic acid (TXA), intraoperative durotomies, procedure length, and length of hospital stay. Complications were classified as either surgically or medically related. Results In the non-syndromic endoscopic group, we experienced 3 (2.1%) surgical and 5 (3.6%) medical complications. In the non-syndromic open group, there were 2 (1.3%) surgical and 7 (4.5%) medical complications. Intraoperative durotomies occurred in 5 (3.6%) endoscopic and 12 (7.8%) open cases, were repaired primarily, and did not result in reoperations for CSF leakage. Syndromic cases resulted in similar complication rates. No mortality or permanent morbidity occurred. Additionally, endoscopic procedures were associated with significantly decreased EBL, transfusions, procedure lengths, and lengths of hospital stay compared to open procedures. Conclusions Rates of intraoperative durotomies, surgical and medical complications were comparable between endoscopic and open techniques. This is the largest direct comparison to date between endoscopic and open interventions for synostosis, and the results are in agreement with previous series that endoscopic surgery confers distinct advantages over open in appropriate patient populations. PMID:26588461

Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

PubMed Central

Stafford, Jason H.; Hirai, Takahisa; Deng, Lei; Chernikova, Sophia B.; Urata, Kimiko; West, Brian L.; Brown, J. Martin

2016-01-01

Background Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell–derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM. Methods To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models. Results GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages. Conclusion CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy. PMID:26538619

Clinical features of congenital portosystemic shunt in children.

PubMed

Kim, Myung Jin; Ko, Jae Sung; Seo, Jeong Kee; Yang, Hye Ran; Chang, Ju Young; Kim, Gi Beom; Cheon, Jung-Eun; Kim, Woo Sun

2012-02-01

Clinical features, images, complications, treatments, and prognosis of 10 children with congenital portosystemic shunt (CPSS) were reviewed. Nine children were diagnosed with intrahepatic shunts while one presented with extrahepatic shunt. CPSS was detected by prenatal ultrasonography in four infants. Three infants presented with galactosemia without an enzyme deficiency. Two children presented with mental retardation and attention deficit hyperactivity disorder. Pulmonary hypertension developed in two patients. Spontaneous closure occurred in four infants with intrahepatic shunts including patent ductus venosus. The shunts were closed using transcatheter embolizations in four patients with intrahepatic shunts. Intrahepatic shunts may close spontaneously. Transcatheter embolization is effective for the treatment of symptomatic intrahepatic shunts.

A prospective study of basal insulin concentrations in dogs with congenital portosystemic shunts.

PubMed

Collings, A J; Gow, A G; Marques, A; Yool, D; Furneaux, R; Mellanby, R; Watson, P J

2012-04-01

Hypoglycaemia is a common cause of morbidity in dogs with congenital portosystemic shunts but the aetiology is unknown. The hypothesis of this study was that dogs with congenital portosystemic shunts would have significantly higher insulin concentrations than dogs without congenital portosystemic shunts. The main objective of the study was to compare peripheral glucose and insulin concentrations between dogs with congenital portosystemic shunts and dogs without congenital portosystemic shunts. Peripheral serum insulin and plasma glucose concentrations were measured in dogs with congenital portosystemic shunts and without congenital portosystemic shunts and compared both between groups as well as to reference intervals derived from healthy dogs. Congenital portosystemic shunts were diagnosed in 41 dogs. Forty-eight dogs hospitalised with other conditions acted as controls. Serum insulin concentrations were mildly elevated (Ä40 μU/mL) in seven dogs and were markedly elevated in two dogs with congenital portosystemic shunts, yet mild hypoglycaemia (3·3 mmol/L) was detected in only one of these dogs. Four dogs with congenital portosystemic shunts showed fasting hypoglycaemia, yet insulin concentrations were within or below the reference interval in three. There was no difference between the median insulin concentration of dogs with congenital portosystemic shunts and without congenital portosystemic shunts. Hyperinsulinaemia is infrequently observed in dogs with congenital portosystemic shunts. The aetiology of hypoglycaemia in dogs with congenital portosystemic shunts merits further investigation. © 2012 British Small Animal Veterinary Association.

Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation after Traumatic Brain Injury in Children

PubMed Central

Newell, Elizabeth; Shellington, David K.; Simon, Dennis W.; Bell, Michael J.; Kochanek, Patrick M.; Feldman, Keri; Bayır, Hülya; Aneja, Rajesh K.; Carcillo, Joseph A.; Clark, Robert S. B.

2015-01-01

Objective The magnitude and role of the cellular immune response following pediatric traumatic brain injury (TBI) remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric TBI by measuring cerebrospinal fluid (CSF) levels of sCD163 and ferritin, and sIL-2Rα, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. Design Retrospective analysis of samples from an established, single-center CSF bank. Setting Pediatric Intensive Care Unit (PICU) in a tertiary Children’s Hospital Patients Sixty-six pediatric patients after severe TBI (Glasgow coma scale score [GCS]<8) age 1 mo-16 y and 17 control patients age 1 mo-14 y. Measurements and Main Results CSF levels of sCD163, ferritin, and sIL-2Rα were determined by ELISA at 2 time points (t1=17±10, t2=72±15 h) for each TBI patient. CSF sCD163, ferritin, and sIL2Rα levels after TBI were compared with controls and analyzed for associations with age, patient sex, initial GCS, diagnosis of abusive head trauma (AHT), the presence of hemorrhage on computerized tomography scan, and Glasgow outcome scale score (GOS). CSF sCD163 was increased in TBI patients at t2 vs. t1 and controls (95.4[21.8–134.0] vs. 31.0[5.7–77.7] and 27.8[19.1–43.1] ng/ml, respectively; median[IQ]; P<0.05). CSF ferritin was increased in TBI patients at t2 and t1 vs. controls (8.3[7.5–19.8] and 8.9[7.5–26.7] vs. [7.5[0.0–0.0] ng/ml, respectively; P<0.05). CSF sIL-2Rα in TBI patients at t2 and t1 were not different vs. controls. Multivariate regression revealed associations between high ferritin and age ≤ 4 y, lower GCS, AHT, and unfavorable GOS. Conclusions Children with TBI demonstrate evidence for macrophage activation after TBI, and in terms of CSF ferritin, this appears more prominent with young age, initial injury severity, AHT, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses, and whether inflammation represents a therapeutic target after TBI. PMID:25850867

The Activin A-Peroxisome Proliferator-Activated Receptor Gamma Axis Contributes to the Transcriptome of GM-CSF-Conditioned Human Macrophages.

PubMed

Nieto, Concha; Bragado, Rafael; Municio, Cristina; Sierra-Filardi, Elena; Alonso, Bárbara; Escribese, María M; Domínguez-Andrés, Jorge; Ardavín, Carlos; Castrillo, Antonio; Vega, Miguel A; Puig-Kröger, Amaya; Corbí, Angel L

2018-01-01

GM-CSF promotes the functional maturation of lung alveolar macrophages (A-MØ), whose differentiation is dependent on the peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor. In fact, blockade of GM-CSF-initiated signaling or deletion of the PPARγ-encoding gene PPARG leads to functionally defective A-MØ and the onset of pulmonary alveolar proteinosis. In vitro , macrophages generated in the presence of GM-CSF display potent proinflammatory, immunogenic and tumor growth-limiting activities. Since GM-CSF upregulates PPARγ expression, we hypothesized that PPARγ might contribute to the gene signature and functional profile of human GM-CSF-conditioned macrophages. To verify this hypothesis, PPARγ expression and activity was assessed in human monocyte-derived macrophages generated in the presence of GM-CSF [proinflammatory GM-CSF-conditioned human monocyte-derived macrophages (GM-MØ)] or M-CSF (anti-inflammatory M-MØ), as well as in ex vivo isolated human A-MØ. GM-MØ showed higher PPARγ expression than M-MØ, and the expression of PPARγ in GM-MØ was found to largely depend on activin A. Ligand-induced activation of PPARγ also resulted in distinct transcriptional and functional outcomes in GM-MØ and M-MØ. Moreover, and in the absence of exogenous activating ligands, PPARγ knockdown significantly altered the GM-MØ transcriptome, causing a global upregulation of proinflammatory genes and significantly modulating the expression of genes involved in cell proliferation and migration. Similar effects were observed in ex vivo isolated human A-MØ, where PPARγ silencing led to enhanced expression of genes coding for growth factors and chemokines and downregulation of cell surface pathogen receptors. Therefore, PPARγ shapes the transcriptome of GM-CSF-dependent human macrophages ( in vitro derived GM-MØ and ex vivo isolated A-MØ) in the absence of exogenous activating ligands, and its expression is primarily regulated by activin A. These results suggest that activin A, through enhancement of PPARγ expression, help macrophages to switch from a proinflammatory to an anti-inflammatory polarization state, thus contributing to limit tissue damage and restore homeostasis.

Post-traumatic hepatic arterial pseudoaneurysm and arterioportal shunt.

PubMed

Maes, J; D'Archambeau, O; Snoeckx, A; Op de Beeck, B; Voormolen, M; Parizel, P M

2010-01-01

The authors report the case of a 21-year-old man who suffered from a blunt abdominal trauma. Initial imaging revealed a liver laceration at the right lobe, a perirenal hematoma of the right kidney and a hematoma of the right adrenal gland. Follow-up MDCT-scan on day 10 after admission showed at the arterial-phase contrast-enhanced study perfusion alterations and two hepatic pseudoaneurysms. The diagnosis of pseudoaneurysm was confirmed and treated angiographically with superselective coil embolization. A follow-up CT-scan on day 17 showed at a nontreated area an arterioportal shunt and a wedge-shaped transient hepatic parenchymal enhancement. This was confirmed angiographically and subsequently treated with coil embolization.

Solar bus regulator and battery charger for IMP's H, I, and J

NASA Technical Reports Server (NTRS)

Paulkovich, J.

1972-01-01

Interplanetary Monitoring Probe (IMP) spacecrafts H, I, and J utilize a direct energy transfer (DET) type of power system operating from a solar array source. A shunt type of regulator prevents the bus voltage from exceeding a preset voltage level. The power system utilizes a single differential amplifier with dual outputs to control the battery charge/shunt regulator and the discharge regulator. A two-voltage level, current limited, series charger and a current sensor control battery state of charge of the silver-cadmium battery pack. Premature termination of the battery charge is prevented by a power available gate that also initiates charge current to the battery upon availability of excess power.

Ventriculoperitoneal shunt - discharge

MedlinePlus

... ventriculoperitoneal - discharge; VP shunt - discharge; Shunt revision - discharge; Hydrocephalus shunt placement - discharge ... Your child has hydrocephalus and needed a shunt placed to drain excess fluid and relieve pressure in the brain. This buildup of brain ...

Should ventriculoatrial shunting be the procedure of choice for normal-pressure hydrocephalus?

PubMed

McGovern, Robert A; Kelly, Kathleen M; Chan, Andrew K; Morrissey, Nicholas J; McKhann, Guy M

2014-06-01

Ventriculoatrial (VA) shunting is rarely used for patients with normal-pressure hydrocephalus (NPH), likely due to surgeon technical preference and case reports indicating cardiopulmonary complications. However, these complications have typically been limited to adults in whom VA shunts had been placed when they were children. Few studies have directly compared VA shunting to ventriculoperitoneal (VP) shunting in cases of NPH. The authors retrospectively analyzed all NPH patients treated by a single surgeon at their center from January 2002 through December 2011. Thirty patients were treated with VA shunts (14 male) and 157 with VP shunts (86 male). The patients' mean age (± SD) at surgery was 73.7 ± 9.4 years for VA shunting and 76.0 ± 8.2 years for VP shunting; the median durations of follow-up were 42.0 months (IQR 19.2-63.6 months) and 34.2 months (IQR 15.8-67.5), respectively. Statistical analysis was performed using chi-square tests and Wilcoxon rank-sum tests. Perioperative and postoperative complications for VA and VP shunting cohorts, respectively, included distal revision (2.7% vs 6.6%, p = 0.45), proximal revision (2.7% vs 2.5%, p = 0.97), and postoperative seizure (2.7% vs 1.5%, p = 0.62). Shunt drainage-related subdural hematomas/hygromas developed in 8.1%/27.0% of VA shunt-treated patients versus 6.6%/26.4% of VP shunt-treated patients (p = 0.76/0.98) and were nearly always successfully managed with programmable-valve adjustment. Symptomatic intracerebral hemorrhage (1.5%) and shunt infection (2.0%) were only observed in those who underwent VP shunting. Of note, no cardiovascular complications were observed in any patient, and there were no cases of distal occlusion of the VA shunt. The authors found no significant differences in complication rates between VA and VP shunting, and VA shunting was not associated with any cardiopulmonary complications. Thus, in the authors' experience, VA shunting is at least as safe as VP shunting for treating NPH.

Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

NASA Technical Reports Server (NTRS)

Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

2015-01-01

Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures.

Portal vein thrombosis and arterioportal shunts: Effects on tumor response after chemoembolization of hepatocellular carcinoma

PubMed Central

Vogl, Thomas J; Nour-Eldin, Nour-Eldin; Emad-Eldin, Sally; Naguib, Nagy NN; Trojan, Joerg; Ackermann, Hans; Abdelaziz, Omar

2011-01-01

AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS. PMID:21455325

Programmable valve shunts: are they really better?

PubMed

Kataria, Rashim; Kumar, Vimal; Mehta, Veer Singh

2012-01-01

Programmable valve shunts allows selection of opening pressure of shunt valve. In the presented article, a unique complication pertaining to programmable shunts has been discussed. A 5-year-old boy who had tectal plate low grade glioma with obstructive hydrocephalus was managed with Codman programmable ventriculoperitoneal shunt. There was a spontaneous change in the opening pressure of the shunt valve leading to shunt malfunction. Routinely used household appliances produce a magnetic field strong enough to cause change in the setting of shunt valve pressure and may lead to valve malfunction. Other causes of programmable valve malfunction also discussed.

Morphology of congenital portosystemic shunts emanating from the left gastric vein in dogs and cats.

PubMed

White, R N; Parry, A T

2013-09-01

To describe the anatomy of congenital portosystemic shunts emanating from the left gastric vein in dogs and cats. A retrospective review of a consecutive series of dogs and cats managed for congenital portosystemic shunts. Forty-six dogs and 27 cats met the inclusion criteria of a congenital portosystemic shunt emanating from the left gastric vein. Of the 46 dogs, 28 (61%) had a shunt that entered the left phrenic vein, 10 (22%) had a shunt that entered the post hepatic caudal vena cava and in 8 (17%) the shunt entered the azygos vein. Of the 27 cats, 19 (70%) had a shunt that entered the left phrenic vein and 8 (30%) had a shunt that entered the post hepatic caudal vena cava. The systemic vein into which the shunt entered was consistent showing three common presentations: left gastro-phrenic, left gastro-caval and left gastro-azygos. This information may help with surgical planning in cases undergoing shunt closure surgery. © 2013 British Small Animal Veterinary Association.

Comparative performance analysis of shunt and series passive filter for LED lamp

NASA Astrophysics Data System (ADS)

Sarwono, Edi; Facta, Mochammad; Handoko, Susatyo

2018-03-01

Light Emitting Diode lamp or LED lamp nowadays is widely used by consumers as a new innovation in the lighting technologies due to its energy saving for low power consumption lamps for brighter light intensity. How ever, the LED lamp produce an electric pollutant known as harmonics. The harmonics is generated by rectifier as part of LED lamp circuit. The present of harmonics in current or voltage has made the source waveform from the grid is distorted. This distortion may cause inacurrate measurement, mall function, and excessive heating for any element at the grid. This paper present an analysis work of shunt and series filters to suppress the harmonics generated by the LED lamp circuit. The work was initiated by conducting several tests to investigate the harmonic content of voltage and currents. The measurements in this work were carried out by using HIOKI Power Quality Analyzer 3197. The measurement results showed that the harmonics current of tested LED lamps were above the limit of IEEE standard 519-2014. Based on the measurement results shunt and series filters were constructed as low pass filters. The bode analysis were appled during construction and prediction of the filters performance. Based on experimental results, the application of shunt filter at input side of LED lamp has reduced THD current up to 88%. On the other hand, the series filter has significantly reduced THD current up to 92%.

Organ distribution of 13N following intravenous injection of [13N]ammonia into portacaval-shunted rats

PubMed Central

Cruz, Nancy F.; Dienel, Gerald A.; Patrick, Tricia A.; Cooper, Arthur J. L.

2016-01-01

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [13N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [13N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 sec) following administration of [13N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2–10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease. PMID:27822667

Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats.

PubMed

Cruz, Nancy F; Dienel, Gerald A; Patrick, Patricia A; Cooper, Arthur J L

2017-06-01

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [ 13 N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [ 13 N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [ 13 N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13 N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2-10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13 N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.

Penile artery shunt syndrome: a novel cause of erectile dysfunction after penile revascularization surgery.

PubMed

Pavlinec, Jonathan G; Hakky, Tariq S; Yang, Christopher; Massis, Kamal; Munarriz, Ricardo; Carrion, Rafael E

2014-09-01

Penile revascularization is a surgical treatment option for erectile dysfunction (ED) in healthy individuals due to a focal arterial occlusion in the absence of generalized vascular disease. Most described failures have been attributed to graft stenosis or disruption of the anastomosis. We report a novel phenomenon called Penile Artery Shunt Syndrome that contributed to persistent ED in a patient after penile microvascular arterial bypass surgery. A 26-year-old man presented for evaluation of long-standing ED, which was attributed to trauma sustained 12 years earlier. He had difficulty obtaining and maintaining erections despite oral pharmacotherapy. Clinical data related to the case were studied, analyzed, and reviewed with urologic and radiologic specialists at multiple centers that collaborated in the care of this patient. Penile duplex ultrasound peak systolic velocities and five-item International Index for Erectile Function questionnaire scores were the main outcome measures. Initial diagnostic workup of the patient confirmed severe insufficiency of the left cavernosal artery, with no evidence of venous leak. The patient underwent penile microvascular arterial bypass surgery with anastomosis of the left inferior epigastric artery to the left dorsal penile artery. The patient had persistence of severe ED despite patent anastomosis by penile duplex ultrasound. Subsequent arteriography revealed an arterial shunt due to an aberrant obturator artery arising from the donor inferior epigastric artery. The patient underwent embolization of the aberrant obturator artery, with resolution of the shunt and marked improvement in erectile function. The presence of an aberrant obturator artery arising from the inferior epigastric artery may predispose to persistent ED after revascularization due to the creation of a shunt phenomenon. Pelvic arteriography may be useful in identifying anomalous anatomic considerations prior to penile revascularization and to evaluate patients with persistent postoperative ED. © 2014 International Society for Sexual Medicine.

Do antibiotic-impregnated shunts in hydrocephalus therapy reduce the risk of infection? An observational study in 258 patients

PubMed Central

Ritz, Rainer; Roser, Florian; Morgalla, Matthias; Dietz, Klaus; Tatagiba, Marcos; Will, Bernd E

2007-01-01

Background Shunt infection in hydrocephalus patients is a severe, even life-threatening complication. Antibiotic-impregnated shunts (AIS) have been developed in an attempt to reduce rate of shunt infection. The study was performed to analyze if AIS can diminish the rate of shunt infection. The pathogenic nature of shunt infection in patients with AIS systems and those without antibiotic impregnated shunts (non-AIS) was compared. Methods Over a period of 24 months in the Department of Neurosurgery at University Hospital of Tübingen shunt surgery was performed in 258 patients. In 86 patients AIS systems were implanted. Shunt catheters were commercially impregnated with clindamycin and rifampicin. Analysis of the clinical data included sex, age, classification of hydrocephalus, shunt types and risk factors for shunt infection [age (< 1 year and > 80 years), prematurely born patients, external ventricular drainage, former shunt infection, former systemic infection, disturbance of consciousness, former radiation-/chemotherapy]. Infection rates and underlying bacterial pathogens of patients with AIS were compared to patients with implanted non-AIS systems (172 patients). Results AIS and non-AIS patients did not differ in sex, etiology of hydrocephalus and the shunt type. In the AIS group 72 out of 86 patients had at least one risk factor (83.7 %), compared to 126 patients in the non-AIS group (73.3 %). There was no significant difference between the two groups (p = 0.0629; Fisher's exact test). In patients with no risk factors, only one patient with non-AIS suffered from shunt infection. In patients with one or more risk factors the rate for shunt infection was 7.14 % in patients with non-AIS and 6.94 % in patients with AIS. Former shunt infection (p = 0.0124) was related to higher risk for shunt infection. The use of AIS had therefore no significant advantage (p = 0.8611; multiple logistic regression). Significantly related to a shunt infection was the number of shunt surgeries. 190 interventions in the AIS group (2.21 interventions per patient) and 408 in the non-AIS group (2.37 interventions per patient) had been performed (p = 0.3063; Wilcoxon). There was no shunt infection in the group of patients on whom only one shunt surgery was performed. In patients with at least two shunt surgeries the infection rate was 9%. The infection rate in AIS patients was 5/52 (9.6 %) and in the non-AIS 10/114 (8.77 %), (p = 1.0; Fisher's exact test). Staphylococcus epidermidis was the most frequent pathogen for shunt infection. Fourteen out of 15 infections occurred within the first 6 months of surgery. The most frequent pathogen for shunt infection was S. epidermidis. No toxic or allergic complications were seen using the AIS shunt systems. The presented data show a remarkably low infection rate of 5.8 % in the non-AIS group compared to other studies which demonstrated a significant decrease in the infection rate by AIS. Conclusion AIS did not significantly reduce shunt infection in hydrocephalus patients in the presented study. In the AIS group three patients suffered from shunt infections caused by skin ulceration or neurosurgical procedures with exposure of the cerebrospinal liquor after shunt implantation. AIS was not developed to prevent infection in such cases, therefore an advantage of AIS can not be excluded. In view of the presented data and the small number of reported studies a prospective randomized multicenter study is required. PMID:17488498

Quantification of the cerebrospinal fluid from a new whole body MRI sequence

NASA Astrophysics Data System (ADS)

Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe

2012-03-01

Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor.

PubMed Central

Høgåsen, A K; Abrahamsen, T G

1993-01-01

Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF. PMID:8478067

Superconducting fault current-limiter with variable shunt impedance

DOEpatents

Llambes, Juan Carlos H; Xiong, Xuming

2013-11-19

A superconducting fault current-limiter is provided, including a superconducting element configured to resistively or inductively limit a fault current, and one or more variable-impedance shunts electrically coupled in parallel with the superconducting element. The variable-impedance shunt(s) is configured to present a first impedance during a superconducting state of the superconducting element and a second impedance during a normal resistive state of the superconducting element. The superconducting element transitions from the superconducting state to the normal resistive state responsive to the fault current, and responsive thereto, the variable-impedance shunt(s) transitions from the first to the second impedance. The second impedance of the variable-impedance shunt(s) is a lower impedance than the first impedance, which facilitates current flow through the variable-impedance shunt(s) during a recovery transition of the superconducting element from the normal resistive state to the superconducting state, and thus, facilitates recovery of the superconducting element under load.

The clinical anatomy of congenital portosystemic venous shunts.

PubMed

Stringer, Mark D

2008-03-01

Congenital portosystemic venous shunts are rare. Their gross anatomy has not been well defined. Four different varieties of congenital portosystemic venous shunts are described in six children seen during a 10-year period, focusing on the anatomy of the shunt as determined by imaging studies and surgery. A detailed review of the literature indicates that congenital portosystemic venous shunts are best classified as: extrahepatic or intrahepatic. Extrahepatic shunts may be further subdivided into portocaval shunts (type 1 end-to-side and type 2 side-to-side) and others. Intrahepatic shunts are due to an abnormal intrahepatic connection between the portal vein and hepatic vein/inferior vena cava or a persistent patent ductus venosus. Additional congenital anomalies, particularly cardiac malformations, may be associated with any type. Some congenital intrahepatic portosystemic venous shunts close spontaneously in infancy; all other congenital portosystemic venous shunts tend to remain patent. To a variable extent, depending largely on the volume and duration of the shunt, affected individuals are at risk of developing hepatic encephalopathy and/or an intrahepatic tumor. The key to understanding the pathogenesis of these shunts lies in the normal developmental mechanisms underlying the formation of the portal vein and inferior vena cava in the embryo. Copyright 2008 Wiley-Liss, Inc.

Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer.

PubMed

Nanjo, Shigeki; Hata, Akito; Okuda, Chiyuki; Kaji, Reiko; Okada, Hideaki; Tamura, Daisuke; Irie, Kei; Okada, Hiroshi; Fukushima, Shoji; Katakami, Nobuyuki

2018-01-01

Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose. T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled. We investigated 13 patients (5 definitive and 8 possible LM cases). In two of the five definitive cases with T790M in and outside the central nervous system (CNS), osimertinib was effective for both lesions, with cerebrospinal fluid (CSF) clearance of cancer cells and sensitive/T790M mutations. In three definitive cases with extra-CNS T790M without CSF T790M, cancer cells and sensitive mutations in the CSF persisted after osimertinib initiation. The median progression-free survival of all 13 patients was 7.2 months. Osimertinib was generally well-tolerated despite poor performance status, but interstitial lung disease (grade 2) was confirmed in one patient. Based on 25 samples from 13 patients, the osimertinib CSF penetration rate was 2.5±0.3%. Osimertinib 80 mg is a useful therapeutic option for refractory LM after classical EGFR-TKI failure. It appears more effective in CSF T790M-positive cases.

Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

PubMed

Sandu, Raluca Elena; Balseanu, Adrian Tudor; Bogdan, Catalin; Slevin, Mark; Petcu, Eugen; Popa-Wagner, Aurel

2017-08-01

Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. Copyright © 2017. Published by Elsevier Inc.

A new cochlear implant electrode with a "cork"-type stopper for inner ear malformations.

PubMed

Sennaroğlu, Levent; Atay, Gamze; Bajin, Münir Demir

2014-08-01

Gusher in inner ear malformations is common in patients with incomplete partition type I and type III. It is also common in less severe form as oozing in incomplete partition type II and large vestibular aqueduct. It is important to prevent cerebrospinal fluid (CSF) escape around the electrode to prevent meningitis. The custom-made device was produced by Med-El Company. It has a "cork"-like stopper instead of the usual silicon ring to prevent gusher. There are two types of electrodes of different lengths. The standard one is 25mm (contact space 1.7mm) and the short one is 20mm (contact space 1.3mm). It was used in 50 patients with different inner ear malformations. Thirteen patients had gusher, and 11 patients oozing during cochleostomy. One patient with initial prototype of the cork electrode had to be revised because of persistent oozing around the electrode. Another patient had slow extrusion of the electrode most probably due to CSF pulsation and had to be revised. Both patients had no more CSF fistula. CSF fistula in inner ear malformations is a serious situation which may lead to recurrent meningitis. The new electrode with "cork" stopper looks promising in preventing the postoperative CSF leak around the electrode. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analysis of signal transduction in cell-free extracts and rafts of Xenopus eggs.

PubMed

Tokmakov, Alexander A; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

2010-05-01

Intracellular signaling during egg activation/fertilization has been extensively studied using intact eggs, which can be manipulated by microinjection of different mRNAs, proteins, or chemical drugs. Furthermore, egg extracts, which retain high CSF activity (CSF-arrested extracts), were developed for studying fertilization/activation signal transduction, which have significant advantages as a model system. The addition of calcium to CSF-arrested extracts initiates a plethora of signaling events that take place during egg activation. Hence, the signaling downstream of calcium mobilization has been successfully studied in the egg extracts. Moreover, despite disruption of membrane-associated signaling compartments and ordered compartmentalization during extract preparation, CSF-arrested extracts can be successfully used to study early signaling events, which occur upstream of calcium release during egg activation/fertilization. In combination with the CSF-arrested extracts, activated egg rafts can reproduce some events of egg activation, including PLCgamma activation, IP3 production, transient calcium release, MAPK inactivation, and meiotic exit. This becomes possible due to complementation of the sperm-induced egg activation signaling machinery present in the rafts with the components of signal transduction system localized in the extracts. Herein, we describe protocols for studying molecular mechanisms of egg fertilization/activation using cell-free extracts and membrane rafts prepared from metaphase-arrested Xenopus eggs.

Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit connected by memristor

PubMed Central

Zhou, Ping; Ahmad, Bashir; Ren, Guodong; Wang, Chunni

2018-01-01

In this paper, a new four-variable dynamical system is proposed to set chaotic circuit composed of memristor and Josephson junction, and the dependence of chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled memristor is used to couple with the RCL-shunted junction circuit, and the dynamical behaviors can be modulated by changing the coupling intensity between the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov exponent are calculated to confirm the emergence of chaos in the improved dynamical system. The outputs and dynamical behaviors can be controlled by the initial setting and external stimulus as well. As a result, chaos can be suppressed and spiking occurs in the sampled outputs under negative feedback, while applying positive feedback type via memristor can be effective to trigger chaos. Furthermore, it is found that the number of multi-attractors in the Jerk circuit can be modulated when memristor coupling is applied on the circuit. These results indicate that memristor coupling can be effective to control chaotic circuits and it is also useful to reproduce dynamical behaviors for neuronal activities. PMID:29342178

Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit connected by memristor.

PubMed

Ma, Jun; Zhou, Ping; Ahmad, Bashir; Ren, Guodong; Wang, Chunni

2018-01-01

In this paper, a new four-variable dynamical system is proposed to set chaotic circuit composed of memristor and Josephson junction, and the dependence of chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled memristor is used to couple with the RCL-shunted junction circuit, and the dynamical behaviors can be modulated by changing the coupling intensity between the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov exponent are calculated to confirm the emergence of chaos in the improved dynamical system. The outputs and dynamical behaviors can be controlled by the initial setting and external stimulus as well. As a result, chaos can be suppressed and spiking occurs in the sampled outputs under negative feedback, while applying positive feedback type via memristor can be effective to trigger chaos. Furthermore, it is found that the number of multi-attractors in the Jerk circuit can be modulated when memristor coupling is applied on the circuit. These results indicate that memristor coupling can be effective to control chaotic circuits and it is also useful to reproduce dynamical behaviors for neuronal activities.

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.

PubMed

Dayon, Loïc; Guiraud, Seu Ping; Corthésy, John; Da Silva, Laeticia; Migliavacca, Eugenia; Tautvydaitė, Domilė; Oikonomidi, Aikaterini; Moullet, Barbara; Henry, Hugues; Métairon, Sylviane; Marquis, Julien; Descombes, Patrick; Collino, Sebastiano; Martin, François-Pierre J; Montoliu, Ivan; Kussmann, Martin; Wojcik, Jérôme; Bowman, Gene L; Popp, Julius

2017-06-17

Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ 1-42 ] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ 1-42 , tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers. We observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers.

Predictors for successful PBSC collection on the fourth day of G-CSF-induced mobilization in allogeneic stem cell donors.

PubMed

van Oostrum, Anja; Zwaginga, Jaap Jan; Croockewit, Sandra; Overdevest, Jacqueline; Fechter, Mirjam; Ruiterkamp, Bart; Brand, Anneke; Netelenbos, Tanja

2017-12-01

Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre-treatment of donors with G-CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G-CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G-CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x10 6 CD34 +/ kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G-CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G-CSF dose correlated positively with CD34 + values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G-CSF scheme increases the yield. © 2017 Wiley Periodicals, Inc.

Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

PubMed

Jessen Krut, Jan; Mellberg, Tomas; Price, Richard W; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.

Predictive factors of bacterial meningitis in the patients seen in emergency departments.

PubMed

Morales-Casado, María Isabel; Julián-Jiménez, Agustín; Lobato-Casado, Paula; Cámara-Marín, Belén; Pérez-Matos, Julio Alberto; Martínez-Maroto, Tamara

2017-04-01

To analyse and compare predictive factors of bacterial meningitis in the patients seen in the Emergency Departments (ED) due to an episode of acute meningitis (AM). A prospective, observational study was carried out in patients aged 15 years and older seen in ED due to AM between August 2009 and November 2015. Thirty-two variables for predicting bacterial meningitis were assessed. They covered epidemiological, comorbidity, clinical and analytical factors. Multivariate logistic regression analysis was performed. The study included 154 patients. The diagnosis was bacterial meningitis in 53 (34.4%) patients. Four variables were significantly associated with bacterial aetiology: cerebrospinal fluid (CSF) lactate concentration ≥33mg/dl (odds ratio [OR] 50.84; 95% confidence interval [CI]: 21.63-119.47, P<.001), serum procalcitonin (PCT) ≥0.8ng/ml (OR 46.34; 95%CI: 19.71-108.89; P<.001), CSF glucose <60% of blood value (OR 20.82; 95%CI: 8.86-48.96; P=.001), CSF polymorphonuclears greater than 50% (OR 20.19; 95%CI: 8.31-49.09; P=.002]. The area under the curve for the model serum PCT≥0.8ng/ml plus CSF lactate ≥33mg/dl was 0.992 (95%CI: 0.979-1; P<.001), and achieved 99% sensitivity and 98% specificity for predicting bacterial meningitis. Serum PCT with CSF lactate, CSF glucose and CSF polymorphonuclears evaluated in an initial assessment in the ED for patients with AM, achieved an excellent diagnostic usefulness for predicting bacterial meningitis. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

MR Angiography Follow-Up 10 Years after Cryptogenic Nonperimesencephalic Subarachnoid Hemorrhage

PubMed Central

Wenz, Holger; Wenz, Ralf; al Mahdi, Mohamad-Motaz; Scharf, Johann; Groden, Christoph; Schmiedek, Peter; Seiz-Rosenhagen, Marcel

2015-01-01

Objectives Long-term magnetic resonance angiography (MRA) follow-up studies regarding cryptogenic nonperimesencephalic subarachnoid hemorrhage (nSAH) are scarce. This single-centre study identified all patients with angiographically verified cryptogenic nSAH from 1998 to 2007: The two main objectives were to prospectively assess the incidence of de novo aneurysm with 3.0-MRI years after cryptogenic nSAH in patients without evidence for further hemorrhage, and retrospectively assess patient demographics and outcome. Methods From prospectively maintained report databases all patients with angiographically verified cryptogenic nSAH were identified. 21 of 29 patients received high-resolution 3T-MRI including time-of-flight and contrast-enhanced angiography, 10.2 ± 2.8 years after cryptogenic nSAH. MRA follow-up imaging was compared with initial digital subtraction angiography (DSA) and CT/MRA. Post-hemorrhage images were related to current MRI with reference to persistent lesions resulting from delayed cerebral ischemia (DCI) and post-hemorrhagic siderosis. Patient-based objectives were retrospectively abstracted from clinical databases. Results 29 patients were identified with cryptogenic nSAH, 17 (59%) were male. Mean age at time of hemorrhage was 52.9 ± 14.4 years (range 4 – 74 years). 21 persons were available for long-term follow-up. In these, there were 213.5 person years of MRI-follow-up. No de novo aneurysm was detected. Mean modified Rankin Scale (mRS) during discharge was 1.28. Post-hemorrhage radiographic vasospasm was found in three patients (10.3%); DCI-related lesions occurred in one patient (3.4%). Five patients (17.2%) needed temporary external ventricular drainage; long-term CSF shunt dependency was necessary only in one patient (3.4%). Initial DSA retrospectively showed a 2 x 2 mm aneurysm of the right distal ICA in one patient, which remained stable. Post-hemorrhage siderosis was detected 8.1 years after the initial bleeding in one patient (4.8%). Conclusion Patients with cryptogenic nSAH have favourable outcomes and do not exhibit higher risks for de novo aneurysms. Therefore the need for long-term follow up after cryptogenic nSAH is questionable. PMID:25688554

Primary ventriculoperitoneal shunting outcomes: a multicentre clinical audit for shunt infection and its risk factors.

PubMed

Woo, P Ym; Wong, H T; Pu, J Ks; Wong, W K; Wong, L Yw; Lee, M Wy; Yam, K Y; Lui, W M; Poon, W S

2016-10-01

To determine the frequency of primary ventriculoperitoneal shunt infection among patients treated at neurosurgical centres of the Hospital Authority and to identify underlying risk factors. This multicentre historical cohort study included consecutive patients who underwent primary ventriculoperitoneal shunting at a Hospital Authority neurosurgery centre from 1 January 2009 to 31 December 2011. The primary endpoint was shunt infection, defined as: (1) the presence of cerebrospinal fluid or shunt hardware culture that yielded the pathogenic micro-organism with associated compatible symptoms and signs of central nervous system infection or shunt malfunction; or (2) surgical incision site infection requiring shunt reinsertion (even in the absence of positive culture); or (3) intraperitoneal pseudocyst formation (even in the absence of positive culture). Secondary endpoints were shunt malfunction, defined as unsatisfactory cerebrospinal fluid drainage that required shunt reinsertion, and 30-day mortality. A primary ventriculoperitoneal shunt was inserted in 538 patients during the study period. The mean age of patients was 48 years (range, 13-88 years) with a male-to-female ratio of 1:1. Aneurysmal subarachnoid haemorrhage was the most common aetiology (n=169, 31%) followed by intracranial tumour (n=164, 30%), central nervous system infection (n=42, 8%), and traumatic brain injury (n=27, 5%). The mean operating time was 75 (standard deviation, 29) minutes. Shunt reinsertion and infection rates were 16% (n=87) and 7% (n=36), respectively. The most common cause for shunt reinsertion was malfunction followed by shunt infection. Independent predictors for shunt infection were: traumatic brain injury (adjusted odds ratio=6.2; 95% confidence interval, 2.3-16.8), emergency shunting (2.3; 1.0-5.1), and prophylactic vancomycin as the sole antibiotic (3.4; 1.1-11.0). The 30-day all-cause mortality was 6% and none were directly procedure-related. This is the first Hong Kong territory-wide review of infection in primary ventriculoperitoneal shunts. Although the ventriculoperitoneal shunt infection rate met international standards, there are areas of improvement such as vancomycin administration and the avoidance of scheduling the procedure as an emergency.

Hepatopulmonary shunting on Tc99m-MAA liver mapping: correlation with dynamic cross-sectional imaging and description of different shunting patterns.

PubMed

Bermo, Mohammed; Matesan, Manuela C; Itani, Malak; Behnia, Fatemeh; Vesselle, Hubert J

2018-04-09

The purpose of the study was to correlate lung shunt fraction (LSF) calculated by intra-arterial injection of Technetium-99m (Tc-99m)-labeled macroaggregated albumin (MAA) in a hepatic artery branch with the presence of certain patterns of vascular shunts on dynamic CT or MRI of the liver. This retrospective study was approved by the institutional review board and informed consent was waived. We reviewed 523 MAA scans in 453 patients (301 men, 152 women) performed from July 2007 to June 2015 and their correlative cross-sectional imaging. Patterns of vascular shunts on dynamic CT or MRI performed within 3 months of the MAA study and that potentially divert hepatic arterial inflow to the systemic venous return were defined as "target shunts." Dynamic CT or MRI was classified into three groups with target shunt present, absent, or indeterminate. The mean LSF was compared across the first and second groups using paired t test. 342 CT and MRI studies met inclusion criteria: target shunts were present in 63 studies, absent in 271 studies, and 8 studies were indeterminate. When target shunts were visualized, the mean LSF on corresponding MAA scans was 12.9 ± 10.36% (95% CI 10.29-15.15%) compared to 4.3 ± 3.17% (95% CI 3.93-4.68%) when no target shunt was visualized. The difference was statistically significant (p value < 0.001). Identified target shunts were either direct (arteriohepatic venous shunt) or indirect (arterioportal shunt combined with a portosystemic shunt). Visualizing certain patterns of vascular shunting on a dynamic CT or MRI scan is associated with high LSF.

Predicting ventriculoperitoneal shunt infection in children with hydrocephalus using artificial neural network.

PubMed

Habibi, Zohreh; Ertiaei, Abolhasan; Nikdad, Mohammad Sadegh; Mirmohseni, Atefeh Sadat; Afarideh, Mohsen; Heidari, Vahid; Saberi, Hooshang; Rezaei, Abdolreza Sheikh; Nejat, Farideh

2016-11-01

The relationships between shunt infection and predictive factors have not been previously investigated using Artificial Neural Network (ANN) model. The aim of this study was to develop an ANN model to predict shunt infection in a group of children with shunted hydrocephalus. Among more than 800 ventriculoperitoneal shunt procedures which had been performed between April 2000 and April 2011, 68 patients with shunt infection and 80 controls that fulfilled a set of meticulous inclusion/exclusion criteria were consecutively enrolled. Univariate analysis was performed for a long list of risk factors, and those with p value < 0.2 were used to create ANN and logistic regression (LR) models. Five variables including birth weight, age at the first shunting, shunt revision, prematurity, and myelomeningocele were significantly associated with shunt infection via univariate analysis, and two other variables (intraventricular hemorrhage and coincided infections) had a p value of less than 0.2. Using these seven input variables, ANN and LR models predicted shunt infection with an accuracy of 83.1 % (AUC; 91.98 %, 95 % CI) and 55.7 % (AUC; 76.5, 95 % CI), respectively. The contribution of the factors in the predictive performance of ANN in descending order was history of shunt revision, low birth weight (under 2000 g), history of prematurity, the age at the first shunt procedure, history of intraventricular hemorrhage, history of myelomeningocele, and coinfection. The findings show that artificial neural networks can predict shunt infection with a high level of accuracy in children with shunted hydrocephalus. Also, the contribution of different risk factors in the prediction of shunt infection can be determined using the trained network.

The Alzheimer’s Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

PubMed Central

Kang, Ju-Hee; Korecka, Magdalena; Figurski, Michal J.; Toledo, Jon B.; Blennow, Kaj; Zetterberg, Henrik; Waligorska, Teresa; Brylska, Magdalena; Fields, Leona; Shah, Nirali; Soares, Holly; Dean, Robert A.; Vanderstichele, Hugo; Petersen, Ronald C.; Aisen, Paul S.; Saykin, Andrew J.; Weiner, Michael W.; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

Introduction We describe Alzheimer’s Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1–42), t-tau, and p-tau181 analytical performance, definition of Alzheimer’s disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. Methods Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1–42, t-tau, and p-tau181 data. Results CSFAD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. Discussion Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials. PMID:26194312

Chiari-like displacement due to spontaneous intracranial hypotension in an adolescent: Successful treatment by epidural blood patch.

PubMed

Schönberger, Jan; Möhlenbruch, Markus; Seitz, Angelika; Bußmann, Cornelia; Bächli, Heidi; Kölker, Stefan

2017-07-01

Spontaneous intracranial hypotension is a rarely diagnosed cause of headache, especially in children and adolescents. It is due to cerebrospinal fluid (CSF) leakage via spinal fistulae occurring without major trauma. An adolescent patient presented with a 3-month history of strictly postural headache. Cranial magnetic resonance imaging (MRI) showed pronounced Chiari-like prolapse of the cerebellar tonsils, narrow ventricles and enlarged cerebral veins. On spinal MRI, myelographic sequences revealed a large collection of CSF around the first sacral roots. CT myelography proved extensive spinal CSF leakage. Hence, we applied epidural patches at multiple levels. Afterwards, symptoms and radiologic findings, including Chiari-like displacement, completely resolved. A Chiari-like descent of the cerebellar tonsils alone does not secure the diagnosis of a Chiari I malformation. Especially if other findings indicate spinal CSF leakage, a systematic work-up should be initiated. In most cases, interventional techniques seal the leak successfully, resulting in a favorable outcome. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

DTIC Science & Technology

2014-03-05

increased granulocyte colony stim- ulating factor (G-CSF) in mouse blood for more than 7 days [7]. The increase was initially believed to be a self ...hematopoietic stem cell mobilization from the bone marrow into the bloodstream. It is involved in recovery from infection [11, 12] and wound healing [13]. Peg-G...mapping data; corrections for the 60Co decay and the small differences in the mass energy absorption coefficients for water and soft tissue were

Use of EOS Low-Dose Biplanar X-Ray for Shunt Series in Children with Hydrocephalus: A Preliminary Study.

PubMed

Ben-Sira, Liat; Shiran, Shelly I; Pratt, Li-Tal; Precel, Ronit; Ovadia, Dror; Constantini, Shlomi; Roth, Jonathan

2018-05-04

Shunt series (SS) are a common diagnostic tool used to verify shunt integrity. SS include X-ray films of the skull, chest, and abdomen and often are performed either when a shunted patient presents with suspected shunt malfunction or as a screening test to identify shunt disconnections or dislodgment. EOS low-dose biplanar X-rays are associated with significantly reduced radiation doses compared with ordinary X-rays and are used for various indications. This is the first publication on the use of EOS as a SS technique. Over a period of 6 months, EOS were performed at our center for various orthopedic indications, mostly for scoliosis evaluation. Nine children (<20 years of age) had a ventriculoperitoneal shunt and served as the study group. We retrospectively reviewed shunt visibility and integrity in the EOS scans as well as regular SS or plain spinal X-rays. Three patients had bilateral shunts, and 8 had previous X-rays for comparison. In all patients, the shunt integrity was easily demonstrated on the EOS images. Two patients had an identified shunt disconnection confirmed on the EOS images. No shunt-related information was missed on the EOS compared with the other X-ray images. These preliminary results suggest that EOS may be used as an alternative technology to demonstrate shunt integrity instead of regular X-ray SS. Favorable shunt visibility without the need for multiple radiation exposures and image processing (such as stitching) results in a significantly shorter examination time and significant less radiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Initial clinical experience of tube-shunt surgery in Ethiopian patients with refractory glaucoma.

PubMed

T/Giorgis, Abeba

2012-04-01

In Ethiopia, it is not uncommon to encounter refractory glaucoma cases that could be managed with tube-shunt surgery. Tube-shunt implant surgery has been a standard procedure option and widely used for various forms of refractory glaucoma. To described the initial experience and outcome of Ahmed Tube shunt implant for refractory adult Ethiopian glaucoma cases. Retrospective review of consecutive adult patients with refractory glaucoma who underwent Ahmed glaucoma valve implant at the Department of ophthalmology, Menelik II Hospital, Addis Ababa between April 2009 and December 2010. intraocular pressure (IOP), visual acuity, use of supplemental medical therapy and surgical complications. Success was defined as IOP greater than 5 and less than 22 mmHg with at least 30% reduction in IOP from preoperative levels with and without supplemental glaucoma medications, no additional surgeries to lower the IOP and without visual loss of light perception from devastating postoperative complications. Thirteen eyes of 12 patients (10 men, 2 women; mean age 52.4 +/- 15. 7) who underwent glaucoma tube-shunt drainage surgery with Ahmed-tube valve were included in this analysis. The mean preoperative IOP was 31.38 +/- 8.67 mmHg with 2.23 +/- 0.44 antiglaucoma medications. Postoperatively, the mean IOP reduced to 15.52 +/- 8.80 mmHg at 1 week, 14.77 +/- 6.39 mmHg at 1 month, 16.62 +/- 4.48 mmHg at 3 months, and 17.15 +/- 3.87 mmHg at 6 months. The reduction from the preoperative mean IOP at last follow up was 45.3% with 1.08 +/- 0.44 supplemental glaucoma medications. The success rate of IOP controlling according to the definition was 76.9%. The pressure remained below 18 mmHg with and without medication in 9/13 (69.2%) eyes, while three eyes required no medication at all till the last follow-up with sustained IOP < 15 mmHg. At the last follow-up the visual acuity reduced by > or = 2 lines in two eyes while one patient's vision worsened from counting finger of one meter to hand movement. Visual improvement of one and two lines documented in two eyes. Hypotony, Tube-corneal touch, acceleration of cataract, choroidal effusion, flat anterior chamber, visual reduction and tube exposure were the types of complications encountered in 6 eyes, while 3 eyes had more than one complication. The study has shown that tube-shunt implant to be effective in lowering intraocular pressure in refractory glaucoma cases. The few cases reported are indicators of the importance of the procedure in salvaging vision of patients with refractory glaucoma and the need of large scale prospective study in the country.

Management Strategies for Hydrocephalus in Alobar Holoprosencephaly: A Case Report and Discussion.

PubMed

Sarica, Can; Yucetas, Cem; Ozen, Ali; Ucler, Necati; Konca, Capan; Akar, Selahattin

2018-06-14

Holoprosencephaly is a rare congenital malformation resulting from an impaired midline division of the prosencephalon into distinct cerebral hemispheres. Hydrocephalus is a frequent problem among the few survivors with alobar holoprosencephaly (aHPE), its most severe form. The literature about neurosurgical management of hydrocephalus in this condition is limited and dispersed, and there are still some points that need to be resolved. We report the case of a newborn with aHPE, hydrocephalus, and central diabetes insipidus. We delineate the complexity of the management of these patients and emphasize the benefits of using an initial programmable shunt valve. Further discussion about management strategies includes reviewing previous reports and the benefits of shunting for hypothalamic osmoreceptor function. © 2018 S. Karger AG, Basel.

Successful preemptive surgical division of type 2-congenital extrahepatic portosystemic shunt in children.

PubMed

Nii, Akira; Takehara, Hiro-o; Kuyama, Hisako; Shimada, Mitsuo

2009-02-01

A congenital extrahepatic portosystemic shunt (CEPS) is a rare abnormality. The shunts are classified into 2 types. Of these, a type 2-shunt is a side-to-side one, which may be treated by a simple shunt division. The aim of this retrospective study was to clarify the effects of a surgical shunt division on 4 children with type 2-CEPS. Between June 2002 and June 2008, 4 children with type 2-CEPS underwent a surgical shunt division. Various clinical factors of each patient, including shunt types, shut ratios evaluated by portal scintigraphy using (123)I-iodoamphetamine, serum levels of ammonia and total bile acids before and after surgery were evaluated. Two children had a conventional open surgery and the other two had a laparoscopic surgery. The serum levels of ammonia as well as total bile acids of these children decreased significantly to the normal levels within a month after the surgical shunt divisions. All the children had a better clinical course. A shunt division, especially by laparoscopic surgery, is an effective therapy for type 2-CEPS. To the best of our knowledge by reviewing literatures, our cases are the youngest ones treated by laparoscopic shunt division.

Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed dog breeds

PubMed Central

2012-01-01

Background An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations. Results Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 – 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of dogs had porto-azygous shunts and 75% had portocaval shunts. Of the dogs with porto-azygous shunts only 27% was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001). Conclusion The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development. PMID:22784395

New and improved ways to treat hydrocephalus: Pursuit of a smart shunt.

PubMed

Lutz, Barry R; Venkataraman, Pranav; Browd, Samuel R

2013-01-01

The most common treatment for hydrocephalus is placement of a cerebrospinal fluid shunt to supplement or replace lost drainage capacity. Shunts are life-saving devices but are notorious for high failure rates, difficulty of diagnosing failure, and limited control options. Shunt designs have changed little since their introduction in 1950s, and the few changes introduced have had little to no impact on these long-standing problems. For decades, the community has envisioned a "smart shunt" that could provide advanced control, diagnostics, and communication based on implanted sensors, feedback control, and telemetry. The most emphasized contribution of smart shunts is the potential for advanced control algorithms, such as weaning from shunt dependency and personalized control. With sensor-based control comes the opportunity to provide data to the physician on patient condition and shunt function, perhaps even by a smart phone. An often ignored but highly valuable contribution would be designs that correct the high failure rates of existing shunts. Despite the long history and increasing development activity in the past decade, patients are yet to see a commercialized smart shunt. Most smart shunt development focuses on concepts or on isolated technical features, but successful smart shunt designs will be a balance between technical feasibility, economic viability, and acceptable regulatory risk. Here, we present the status of this effort and a framework for understanding the challenges and opportunities that will guide introduction of smart shunts into patient care.

Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed dog breeds.

PubMed

Van den Bossche, Lindsay; van Steenbeek, Frank G; Favier, Robert P; Kummeling, Anne; Leegwater, Peter A J; Rothuizen, Jan

2012-07-11

An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations. Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 - 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of dogs had porto-azygous shunts and 75% had portocaval shunts. Of the dogs with porto-azygous shunts only 27% was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001). The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development.

Over-drainage and persistent shunt-dependency in patients with idiopathic intracranial hypertension treated with shunts and bariatric surgery.

PubMed

Roth, Jonathan; Constantini, Shlomi; Kesler, Anat

2015-01-01

Idiopathic intracranial hypertension (IIH) may lead to visual impairment. Shunt surgery is indicated for refractory IIH-related symptoms that persist despite medical treatment, or those presenting with significant visual decline. Obesity is a risk factor for IIH; a reduction in weight has been shown to improve papilledema. Bariatric surgery (BS) has been suggested for treating IIH associated with morbid obesity. In this study, we describe a high rate of over-drainage (OD) seen in patients following shunts and BS. The study cohort includes 13 patients with IIH that underwent shunt surgery for treatment of the IIH-related symptoms. Six patients underwent BS in addition to the shunt surgery (but not concomitantly). Seven patients had only shunt surgeries with no BS. Data were collected retrospectively. BS effectively led to weight reduction (body mass index decreasing from 43 ± 4 to 28 ± 5). Patients undergoing BS had 1-6 (2.5 ± 1.9) shunt revisions for OD following BS, as opposed to 0-3 (1.4 ± 1.1) revisions prior to BS over similar time spans (statistically insignificant difference), and 0-6 (1.6 ± 2.5) revisions among the non-BS patients over a longer time span (statistically insignificant difference). Two patients in the BS group underwent shunt externalization and closure; however, they proved to be shunt-dependent. Patients with IIH that undergo shunt surgery and BS (not concomitantly) may suffer from OD symptoms, necessitating multiple shunt revisions, and valve upgrades. Despite BS being a valid primary treatment for some patients with IIH, among shunted patients, BS may not lead to resolution of IIH-related symptoms and patients may remain shunt-dependent.

Outcome of shunting in idiopathic normal-pressure hydrocephalus and the value of outcome assessment in shunted patients.

PubMed

Klinge, Petra; Marmarou, Anthony; Bergsneider, Marvin; Relkin, Norman; Black, Peter McL

2005-09-01

To develop guidelines for assessing shunt outcome in patients with idiopathic normal-pressure hydrocephalus (INPH). To date, the literature available on this topic has been marked by disparate definitions of clinical improvement, varying postoperative follow-up protocols and periods, and substantial differences in the postoperative management. Because specific criteria for defining clinical improvement are seldom reported, conclusions drawn about shunt outcome may be subjective. A MEDLINE search back to 1966 was undertaken using the query NPH, normal-pressure hydrocephalus, shunting, shunt treatment, shunt response, outcome, and clinical outcome. The criteria for selection were studies that included INPH from 1966 to the present in which the outcome of INPH was reported in patient groups of 20 or more. To date, there is no standard for outcome assessment of shunt treatment in INPH. The variable improvement rates reported are not only because of different criteria for selection of patients but also because of different postoperative assessment procedures and follow-up intervals. Studies that have established fixed protocols for follow-up have shown that short- and long-term periods after shunting are determined by many factors. Whereas short-term results were more likely to be influenced by shunt-associated risks, long-term results were independent of factors inherent to the shunt procedure and shunt complications, i.e., death and morbidity related to concomitant cerebrovascular and vascular diseases. Studies have shown that beyond 1 year after surgery, these factors definitely influence the clinical effect of shunting, making the 1-year postshunt period a potential determinant of the shunt outcome. Guidelines for outcome assessment were developed on the basis of the available evidence and consensus of expert opinion.

29 CFR 1926.906 - Initiation of explosive charges-electric blasting.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dangerous. Blasting cap leg wires shall be kept short-circuited (shunted) until they are connected into the..., in accordance with the manufacturer's recommendations. (f) Connecting wires and lead wires shall be... manufacturer of the electric blasting caps used. (o) The number of electric blasting caps connected to a...

Evaluation of Mismatch Losses due to Shunts in industrial Silicon Photovoltaic Modules

NASA Astrophysics Data System (ADS)

Somasundaran, P.; Shilpi, M.; Gupta, R.

2017-05-01

In order to achieve higher efficiencies in photovoltaic module technology, it is important to characterize the shunts and other defects which degrade the performance of cells and modules as well as decrease their efficiency. These shunts also affect the reliability of cells and modules. It is important to understand how much fill factor and power loss is caused by the presence of shunts in the module. Shunts not only reduce the module power output, but also affect the I-V characteristics of the cell and hence the characteristics of the shunted cells are different from those of the shunt-free cells connected in the module leading to the mismatch effect. This is an interesting effect which has been systematically investigated in the present work. Moreover, the flow of increased shunt current will give rise to increased temperature in the region of shunt, which will affect the cell and hence module performance. In the present study, the distributed diode model has been extended to the module level and applied to evaluate the electrical mismatch losses and thermal mismatch losses due to shunts in industrial Silicon PV modules.

Measurements of left-to-right intracardiac shunting in adults: oximetric versus indicator dilution techniques.

PubMed

Hillis, L D; Winniford, M D; Jackson, J A; Firth, B G

1985-01-01

Of the various techniques that are available to assess the presence and magnitude of intracardiac shunting, oximetry and indicator dilution are used most frequently. This study was performed to compare these methods in adult patients with pure left-to-right intracardiac shunting. In 27 patients [12 men, 15 women, aged 32 +/- 12 (mean +/- SD) years], shunt magnitude was assessed in close temporal proximity by both techniques. The oximetric percentage left-to-right shunt averaged 55 +/- 16%, whereas the indocyanine green dye percentage shunt was significantly less (36 +/- 14%, p less than 0.001). The oximetric percentage shunt exceeded the indocyanine green dye percentage shunt in 26 and did so by greater than 20% in 23 patients. Thus, there is a substantial difference in shunt magnitude between the oximetric and the indicator dilution techniques. In infants, indicator dilution yields results that are larger than those obtained with the oximetric method. Conversely, in adults, the indicator dilution technique gives results that are consistently smaller than those obtained with oximetry. As a result, the decision regarding therapy of an intracardiac shunt should be made with this in mind.

Lower rates of symptom recurrence and surgical revision after primary compared with secondary endoscopic third ventriculostomy for obstructive hydrocephalus secondary to aqueductal stenosis in adults.

PubMed

Sankey, Eric W; Goodwin, C Rory; Jusué-Torres, Ignacio; Elder, Benjamin D; Hoffberger, Jamie; Lu, Jennifer; Blitz, Ari M; Rigamonti, Daniele

2016-05-01

OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for obstructive hydrocephalus; however, the success of ETV in patients who have previously undergone shunt placement remains unclear. The present study analyzed 103 adult patients with aqueductal stenosis who underwent ETV for obstructive hydrocephalus and evaluated the effect of previous shunt placement on post-ETV outcomes. METHODS This study was a retrospective review of 151 consecutive patients who were treated between 2007 and 2013 with ETV for hydrocephalus. One hundred three (68.2%) patients with aqueductal stenosis causing obstructive hydrocephalus were included in the analysis. Postoperative ETV patency and aqueductal and cisternal flow were assessed by high-resolution, gradient-echo MRI. Post-ETV Mini-Mental State Examination, Timed Up and Go, and Tinetti scores were compared with preoperative values. Univariate and multivariate analyses were performed comparing the post-ETV outcomes in patients who underwent a primary (no previous shunt) ETV (n = 64) versus secondary (previous shunt) ETV (n = 39). RESULTS The majority of patients showed significant improvement in symptoms after ETV; however, no significant differences were seen in any of the quantitative tests performed during follow-up. Symptom recurrence occurred in 29 (28.2%) patients after ETV, after a median of 3.0 (interquartile range 0.8-8.0) months post-ETV failure. Twenty-seven (26.2%) patients required surgical revision after their initial ETV. Patients who received a secondary ETV had higher rates of symptom recurrence (p = 0.003) and surgical revision (p = 0.003), particularly in regard to additional shunt placement/revision post-ETV (p = 0.005). These differences remained significant after multivariate analysis for both symptom recurrence (p = 0.030) and surgical revision (p = 0.043). CONCLUSIONS Patients with obstructive hydrocephalus due to aqueductal stenosis exhibit symptomatic improvement after ETV, with a relatively low failure rate. Patients with a primary history of shunt placement who undergo ETV as a secondary intervention are at increased risk of symptom recurrence and need for surgical revision post-ETV.

Passively Shunted Piezoelectric Damping of Centrifugally-Loaded Plates

NASA Technical Reports Server (NTRS)

Duffy, Kirsten P.; Provenza, Andrew J.; Trudell, Jeffrey J.; Min, James B.

2009-01-01

Researchers at NASA Glenn Research Center have been investigating shunted piezoelectric circuits as potential damping treatments for turbomachinery rotor blades. This effort seeks to determine the effects of centrifugal loading on passively-shunted piezoelectric - damped plates. Passive shunt circuit parameters are optimized for the plate's third bending mode. Tests are performed both non-spinning and in the Dynamic Spin Facility to verify the analysis, and to determine the effectiveness of the damping under centrifugal loading. Results show that a resistive shunt circuit will reduce resonant vibration for this configuration. However, a tuned shunt circuit will be required to achieve the desired damping level. The analysis and testing address several issues with passive shunt circuit implementation in a rotating system, including piezoelectric material integrity under centrifugal loading, shunt circuit implementation, and tip mode damping.

Automatic Railway Traffic Object Detection System Using Feature Fusion Refine Neural Network under Shunting Mode.

PubMed

Ye, Tao; Wang, Baocheng; Song, Ping; Li, Juan

2018-06-12

Many accidents happen under shunting mode when the speed of a train is below 45 km/h. In this mode, train attendants observe the railway condition ahead using the traditional manual method and tell the observation results to the driver in order to avoid danger. To address this problem, an automatic object detection system based on convolutional neural network (CNN) is proposed to detect objects ahead in shunting mode, which is called Feature Fusion Refine neural network (FR-Net). It consists of three connected modules, i.e., the depthwise-pointwise convolution, the coarse detection module, and the object detection module. Depth-wise-pointwise convolutions are used to improve the detection in real time. The coarse detection module coarsely refine the locations and sizes of prior anchors to provide better initialization for the subsequent module and also reduces search space for the classification, whereas the object detection module aims to regress accurate object locations and predict the class labels for the prior anchors. The experimental results on the railway traffic dataset show that FR-Net achieves 0.8953 mAP with 72.3 FPS performance on a machine with a GeForce GTX1080Ti with the input size of 320 × 320 pixels. The results imply that FR-Net takes a good tradeoff both on effectiveness and real time performance. The proposed method can meet the needs of practical application in shunting mode.

Long-term survival in a dog with meningoencephalitis and epidural abscessation due to Actinomyces species.

PubMed

Song, Rachel B; Vitullo, Carina A; da Costa, Ronaldo C; Daniels, Joshua B

2015-07-01

A 2-year-old, female spayed Golden Retriever dog was presented to The Ohio State University Veterinary Medical Center for evaluation of ataxia, cervical pain, 1 episode of acute collapse, dull mentation, and inappetence. Physical examination revealed an elevated temperature of 39.7°C and severe cervical pain. Blood work revealed a mature neutrophilia. Cerebrospinal fluid (CSF) analysis revealed nondegenerative neutrophilic pleocytosis with no infectious agents. A presumptive diagnosis of steroid-responsive meningitis-arteritis was made, and corticosteroid therapy was started. The patient improved initially but experienced a vestibular episode characterized by falling and vertical nystagmus. A magnetic resonance imaging of the brain revealed an epidural abscess in the cervical vertebral canal and diffuse meningeal enhancement in the brain and cranial cervical spine. Abscess drainage revealed degenerate neutrophils and several filamentous, branching organisms. Culture of the initial CSF using an enrichment broth revealed growth of a Gram-positive organism 5 days after fluid collection. The isolate was identified by partial 16S ribosomal DNA sequencing as Actinomyces spp. The patient was successfully treated with long-term antibiotics. Our study reports the long-term survival after medical treatment of bacterial meningoencephalitis and epidural abscessation due to Actinomyces sp. infection in a dog. Bacterial meningoencephalitis should be included as a differential diagnosis in patients with cervical pain and fever, even when a nondegenerative neutrophilic pleocytosis is found on CSF analysis. Culture of the CSF with use of an enrichment broth should be considered in all cases of neutrophilic pleocytosis to rule out infections of the central nervous system. © 2015 The Author(s).

Demonstration of uneven distribution of intracranial pulsatility in hydrocephalus patients.

PubMed

Eide, Per K

2008-11-01

Data from intracranial pressure (ICP) recordings in patients with hydrocephalus were reviewed to determine whether intracranial pulsatility within the cerebrospinal fluid (CSF) of cerebral ventricles (ICP(LV)) may differ from that within the brain parenchyma (ICP(PAR)), and whether pulsatility may differ between noncommunicating ventricles. The authors retrieved data from recordings previously obtained in 7 patients with hydrocephalus (noncommunicating in 4 and communicating in 3) and shunt failure who received both an external ventricular drainage (EVD) and an ICP sensor as part of surveillance during intensive care. Simultaneous ICP(LV) and ICP(PAR) signals were available in 6 cases, and simultaneous signals from the lateral and fourth ventricles (ICP(LV) and ICP4V, respectively) were recorded in 1 case. The recordings with both signals were parsed into 6-second time windows. Pulsatility was characterized by the wave amplitude and rise time coefficient, and differences in pulsatility between the ICP(LV) and ICP(PAR) signals (6 cases) or ICP(LV) and ICP4V signals (1 case) were determined. There was uneven distribution of intracranial pulsatility in all 7 patients, shown as significantly elevated pulsatility (that is, higher wave amplitudes and rise time coefficients) within the ventricles (ICP(LV)) than within brain parenchyma (ICP(PAR)) in 6 patients, and significantly higher pulsatility in the fourth (ICP4V) than in the lateral (ICP(LV)) ventricles in 1 patient. Differences > or = 1 mm Hg in ICP wave amplitude were found in 0.5-100% (median 9.4%) of observations in the 7 patients (total number of 6-second time windows, 68,242). The present observations demonstrate uneven distribution of intracranial pulsatility in patients with hydrocephalus, higher pulse pressure amplitudes within the ventricular CSF (ICP(LV)) than within the brain parenchyma (ICP(PAR)). This may be one mechanism behind ventricular enlargement in hydrocephalus.

The Dandy-Walker malformation. A review of 40 cases.

PubMed

Hirsch, J F; Pierre-Kahn, A; Renier, D; Sainte-Rose, C; Hoppe-Hirsch, E

1984-09-01

Forty cases of Dandy-Walker malformation referred to the Hôpital Necker Enfants-Malades between 1969 and 1982 have been reviewed. The incidence of the malformation in hydrocephalus was 2.4%. There was a slight, statistically insignificant, female prevalence. Hydrocephalus should not be included in the definition of the syndrome. In 80% of the cases, it was actually a post-natal complication of the malformation and most often developed within 3 months after birth. In 80% of the cases, a communication, although insufficient, was found between the dilated 4th ventricle and the subarachnoid space. Since this communication is probably established through the foramina of Luschka, the definition of the Dandy-Walker malformation should only include atresia of the foramen of Magendie. Associated brain and systemic malformations were numerous. Among facial anomalies, facial angiomas were found in 10% of our cases. The association of facial and cardiovascular anomalies favors the hypothesis that the onset of the malformation occurs between the formation and the migration of the cells of the neural crest (that is, between the 3rd and the 4th post-ovulatory week, earlier than previously thought). Except in selected patients, membrane excision has a high rate of failure and should be abandoned. Cyst-peritoneal shunting avoids the risk of an entrapped fourth ventricle and is presently the best surgical procedure. The overall mortality in this series was 12.5%. Intelligence quotients were over 80 in 60% of the patients. Other studies will be necessary to understand why the communication between the fourth ventricle and the subarachnoid spaces, sufficient in utero, usually becomes insufficient for a normal cerebrospinal fluid (CSF) circulation in the first months following birth. Two hypotheses are discussed: a change in CSF circulation, or bleeding in the dilated fourth ventricle during delivery.

Intraventricular Neurocysticercosis: Experience and Long-Term Outcome from a Tertiary Referral Center in the United States.

PubMed

Nash, Theodore E; Ware, JeanAnne M; Mahanty, Siddhartha

2018-04-23

Ventricular involvement in neurocysticercosis (NCC), a common serious manifestation of NCC, has distinct clinical presentations, complications, and treatments primarily because of partial or complete obstruction of the cerebrospinal fluid (CSF) flow by Taenia solium cysts. We review the clinical course, treatments, and long-term outcomes in 23 of 121 (19.0%) total NCC patients with ventricular cysts referred to the National Institutes of Health from 1985 to the October 2017. Patients had a median age of 31.8 (range: 22.4-52.6 years), were 60.9% male, diagnosed a median of 6.5 years (range: 0.17-16 years) after immigration, and were followed for a median of 3.6 years (range: 0.1-30.5 years). Other forms and manifestations of NCC were present in 73.9% (17/23). The fourth ventricle was involved in a majority (15/23, 65.2%) resulting in hydrocephalus (73.9%), ventriculitis, and periventricular edema (7/23, 30.4%). Cystectomy was accomplished in 60.9%, usually by removal of a fourth ventricular cyst through a suboccipital craniotomy. Nonresectable cysts were treated medically. Ventriculoperitoneal shunts were inserted in 43.5% (10/23) and failed in four, three from infection. Other complications included surgically induced injuries (4/23, 17.4%) and entrapment of a lateral ventricle (2/23, 8.7%). Despite a common severe early course, 90.9% (20/22) stabilized without recurrence, 15% (3/20) complained of mild-to-moderate neurological complaints, and 15% (3/20) were significantly disabled. Four patients who underwent removal of ventricular cysts without significant other NCC and who received with no cysticidal treatment became CSF cestode antigen negative without recurrence indicating that after successful extraction of cysts, additional cysticidal treatment may not be needed.

Overdrainage of cerebrospinal fluid caused by detachment of the pressure control cam in a programmable valve after 3-tesla magnetic resonance imaging.

PubMed

Watanabe, Atsushi; Seguchi, Tatsuya; Hongo, Kazuhiro

2010-02-01

The authors report a rare case of overdrainage of the CSF caused by the malfunction of a Codman-Hakim programmable valve (CHPV) following a 3-T MR imaging procedure. Nine years ago this 72-year-old woman underwent ventriculoperitoneal shunt placement with a CHPV system for hydrocephalus due to subarachnoid hemorrhage. The postoperative course was uneventful and the system functioned well. A radiograph obtained immediately after 3-T MR imaging revealed that the pressure control cam in the valve system was detached from the base plate. Intracranial hypotension syndrome occurred several hours after the MR imaging study, and a CT scan revealed a decrease in ventricle size. A revision of the system promptly resolved the symptoms, and a postoperative CT scan revealed that the ventricle size was restored to normal. Examination of the extracted valve showed a Y-shaped crack in the plastic housing as well as detachment of the white marker and cam from the base plate. A reduction in the power of the flat spring to press the valve ball led to CSF overdrainage because of a loss of support by the cam. Because the patient had incurred no head injury during the day and radiographic studies of the system 5 years previously had shown detachment of the white marker, damage to the system might have been caused by a past impact. These facts may indicate that the antimagnetic performance of the system could have decreased due to a previous impact and that the strong magnetic force in a 3-T MR imaging environment might have caused detachment of the cam.

Influence of general anaesthesia on slow waves of intracranial pressure.

PubMed

Lalou, Despina A; Czosnyka, Marek; Donnelly, Joseph; Lavinio, Andrea; Pickard, John D; Garnett, Matthew; Czosnyka, Zofia

2016-07-01

Slow vasogenic intracranial pressure (ICP) waves are spontaneous ICP oscillations with a low frequency bandwidth of 0.3-4 cycles/min (B-waves). B-waves reflect dynamic oscillations in cerebral blood volume associated with autoregulatory cerebral vasodilation and vasoconstriction. This study quantifies the effects of general anaesthesia (GA) on the magnitude of B-waves compared to natural sleep and conscious state. The magnitude of B-waves was assessed in 4 groups of 30 patients each with clinical indications for ICP monitoring. Normal pressure hydrocephalus patients undergoing Cerebrospinal Fluid (CSF) infusion studies in the conscious state (GROUP A) and under GA (GROUP B), and hydrocephalus patients undergoing overnight ICP monitoring during physiological sleep (GROUP C) were compared to deeply sedated traumatic brain injury (TBI) patients with well-controlled ICP during the first night of Intensive Care Unit (ICU) stay (GROUP D). A total of 120 patients were included. During CSF infusion studies, the magnitude of slow waves was higher in conscious patients ( 0.23+/-0.10 mm Hg) when compared to anaesthetised patients ( 0.15+/-0.10 mm Hg; p = 0.011). Overnight magnitude of slow waves was higher in patients during natural sleep (GROUP C: 0.20+/-0.13 mm Hg) when compared to TBI patients under deep sedation (GROUP D: 0.11+/- 0.09 mm Hg; p = 0.002). GA and deep sedation are associated with a reduced magnitude of B-waves. ICP monitoring carried out under GA is affected by iatrogenic suppression of slow vasogenic waves of ICP. Accounting for the effects of anaesthesia on vasogenic waves may prevent the misidentification of potential shunt-responders as non-responders.

Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism

PubMed Central

Jumpertz, Reiner; Guijarro, Ana; Pratley, Richard E.; Mason, Clinton C.; Piomelli, Daniele; Krakoff, Jonathan

2012-01-01

Rodent experiments have emphasized a role of central fatty acid (FA) species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF) and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT) followed by measurements of 24 hour (24EE) and sleep energy expenditure (SLEEP) as well as respiratory quotient (RQ) in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid) concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16∶1, C18∶1) and very-long-chain saturated (C24∶0, C26∶0) FAs. Conclusions: Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis. PMID:22911803

Baclofen Solution for Low-Volume Therapeutic Delivery.

PubMed

Meythaler, Jay M; Peduzzi, Jean D

2017-06-01

Baclofen is a zwitterion molecule where increased ions in the excipient increase the solubility. We developed baclofen in a stable solution similar to cerebrospinal fluid (CSF) without bicarbonate and proteins to improve the solubility of the baclofen and to reduce the potential toxicity to the central nervous system (CNS) and subarachnoid space. The objective is to develop a solution of baclofen wherein baclofen is solubilized in a multivalent physiological ion solution such as artificial cerebrospinal fluid (aCSF) at a concentration from 2 mg/cc to 10 mg/cc. First, to determine the solubility of Baclofen in aCSF, solubility was determined at six different pH levels at 37°C, by the addition of aCSF to a known amount of Baclofen. The final concentrations were confirmed by high performance liquid chromatography (HPLC) analysis. Second, the stability of Baclofen at 4 mg/cc investigated in a test manufacturing batch utilizing standard methods of production of 1500 20 cc vials inverted for 18 months at 25°C at 60% humidity. The stability and purity of the baclofen was verified at 18 months by HPLC analysis. Baclofen was initially soluble between pH of 6-8 above 7 mg/cc but fell back to 6.3-5.8 mg/cc level with time. Baclofen produced in vials with inversion were noted to be stable at 4 mg/cc at 18 months with less than 2% breakdown of the baclofen in solution. Baclofen is much more soluble in artificial CSF than normal saline. The artificial CSF may also be less toxic to the subarachnoid space than saline. © 2016 International Neuromodulation Society.

Peroxiredoxin VI Oxidation in Cerebrospinal Fluid Correlates with TBI Outcome

PubMed Central

Manevich, Y.; Hutchens, S.; Halushka, P.V.; Tew, K.D.; Townsend, D. M.; Jauch, E.C.; Borg, K.

2014-01-01

Traumatic brain injury (TBI) patients would benefit from the identification of reliable biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant stress-mediated damage progression after hospital admission and subsequent ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients, and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner glutathione S-transferase pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) under TBI. Furthermore, significant and progressive oxidation of “buried” protein thiol in CSF of TBI patients (as compared to that of non-trauma control) were detected over a 24h period following hospital admission, with increased oxidation correlating with severity of trauma. Conversely, recovery of Prdx6 activity after 24h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a biomarker for TBI outcome and a future indicator of therapeutic efficacy. PMID:24726861

Combined Endoscopic Transorbital and Endonasal Repair of High Flow Orbital Apex/Middle Fossa Cerebrospinal Fluid Leak with a Nasoseptal Flap.

PubMed

Lucke-Wold, Brandon; Mendez, Gustavo; Cua, David; Akins, Paul; Gillham, Haley; Ciporen, Jeremy

2018-01-01

High flow orbital apex or middle fossa cerebrospinal fluid (CSF) leaks can be life threatening and complex to repair. These leaks associated with large dural defects are most commonly repaired with an open temporalis muscle patch or free flaps, but these flaps do not always stop the leak. A 65-year-old patient presented two years after orbital exenteration and radiation for squamous cell carcinoma. He developed multi-organism meningitis and pneumocephalus secondary to a large high-flow orbital apex/middle fossa CSF leak. To repair the leak, a combined endoscopic transorbital/endonasal approach with pedicled nasospetal flap and dermis fat graft was used. We describe the unique endoscopic technique that was used to treat the life threatening high flow orbital apex/middle fossa CSF leak. The technique allowed the use of the transposed pedicled flap, which is an alternative to the free flap in controlling CSF leak. Cisternogram post-operatively and clinical exam confirmed resolution of CSF leak. Although a critically ill patient at admission with a modified Rankin scale (MRS) of 5, he was discharged home on continued IV antibiotic therapy with a MRS of 3. Endoscopic evaluation at three months after treatment showed the effectiveness of the flap and he continued to improve clinically. This is the first case to describe a combined endoscopic transorbital and endonasal repair of high flow orbital apex/middle fossa CSF leak with a pedicled nasoseptal flap. These techniques can be utilized during initial reconstruction after orbital exenteration or as a salvage flap.

Immunophenotyping of the cerebrospinal fluid as a prognostic factor at diagnosis of acute lymphoblastic leukemia in children and adolescents.

PubMed

Cancela, Camila Silva Peres; Murao, Mitiko; Assumpção, Juliana Godoy; Souza, Marcelo Eduardo de Lima; de Macedo, Antonio Vaz; Viana, Marcos Borato; De Oliveira, Benigna Maria

2017-03-01

This study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p < 0.0001) and event-free survival (p < 0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.

Shunt diameter in agenesis of the ductus venosus with extrahepatic portosystemic shunt impacts on prognosis.

PubMed

Shen, O; Valsky, D V; Messing, B; Cohen, S M; Lipschuetz, M; Yagel, S

2011-02-01

Agenesis of the ductus venosus (ADV) is a rare condition in which there are two variants of umbilical vein drainage: intrahepatic shunt or extrahepatic (portosystemic) shunt. It has been posited that the extrahepatic variant carries a poorer prognosis. However, in the absence of associated anomalies there is still a wide variation in outcome. We evaluated the portal system in cases of ADV and aimed to identify parameters that might predict outcome. We conducted a retrospective study of cases of ADV with extrahepatic shunt that had been examined in two centers, and collected new cases prospectively. The route of the shunt was depicted using two-dimensional (2D) and three-dimensional (3D) ultrasound imaging. In an attempt to characterize portal system and shunt developmental variations and their possible impact on outcome, the diameter of the shunt was compared with the diameter of the umbilical vein and the entire portal vasculature was assessed. Poor outcome was defined as persistent morbidity or fetal or neonatal death. Twenty-two cases of ADV were identified: nine retrospectively and 13 prospectively. Aberrant shunts from the umbilical vein were identified to the right atrium, coronary sinus, inferior vena cava (IVC) and iliac vein. In seven of 22 cases (32%) a wide connection was observed. In six of these seven cases (86%) the outcome was poor, including four with severe associated anomalies and two with hepatic dysfunction. In five of these cases, cardiomegaly with tricuspid regurgitation was observed, as well as underdevelopment of the portal system. In only five of 15 cases with a narrow shunt (33%) was the outcome poor, and in all five cases the poor outcome was related to associated anomalies. In cases of ADV with extrahepatic shunt, portal system development is impacted by the diameter of the shunt. If the shunt is narrow, the portal system will have developed normally. A wide shunt is associated with underdevelopment or absence of the portal system. In cases of ADV with extrahepatic shunt, prognosis is determined by the severity of associated anomalies, the diameter of the shunt and development of the portal system. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Internal carotid artery rupture caused by carotid shunt insertion

PubMed Central

Illuminati, Giulio; Caliò, Francesco G.; Pizzardi, Giulia; Vietri, Francesco

2015-01-01

Introduction Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. Presentation of case A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Discussion Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Conclusion Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. PMID:26255001

Estimating the scale of adverse animal welfare consequences of movement restriction and mitigation strategies in a classical swine fever outbreak.

PubMed

Yadav, Shankar; Weng, Hsin-Yi

2017-04-04

The study aim was to quantify the impact of movement restriction on the well-being of pigs and the associated mitigation responses during a classical swine fever (CSF) outbreak. We developed a stochastic risk assessment model and incorporated Indiana swine industry statistics to estimate the timing and number of swine premises that would encounter overcrowding or feed interruption resulting from movement restriction. Our model also quantified the amount of on-farm euthanasia and movement of pigs to slaughter plants required to alleviate those conditions. We simulated various single-site (i.e., an outbreak initiated from one location) and multiple-site (i.e., an outbreak initiated from more than one location) outbreak scenarios in Indiana to estimate outputs. The study estimated that 14% of the swine premises in Indiana would encounter overcrowding or feed interruption due to movement restriction implemented during a CSF outbreak. The number of premises that would experience animal welfare conditions was about 2.5 fold of the number of infected premises. On-farm euthanasia needed to be performed on 33% of those swine premises to alleviate adverse animal welfare conditions, and more than 90% of on-farm euthanasia had to be carried out within 2 weeks after the implementation of movement restriction. Conversely, movement of pigs to slaughter plants could alleviate 67% of adverse animal welfare conditions due to movement restriction, and only less than 1% of movement of pigs to slaughter plants had to be initiated in the first 2 weeks of movement restrictions. The risk of secondary outbreaks due to movement of pigs from movement restriction areas to slaughter plants was low and only seven pigs from each shipment needed to be tested for CSF infection to prevent a secondary outbreak. We found that the scale of adverse animal welfare consequences of movement restriction during a CSF outbreak in Indiana was substantial, and controlled movement of pigs to slaughter plants was an efficient and low-risk alternative mitigation response to on-farm euthanasia. The output estimates generated from this study provide empirical evidence for decision makers to properly incorporate required resources for mitigating adverse animal welfare conditions in CSF outbreak management strategic planning.

Cellular changes in motor neuron cell culture produced by cytotoxic cerebrospinal fluid from patients with amyotrophic lateral sclerosis.

PubMed

Gomez-Pinedo, U; Yáñez, M; Matías-Guiu, J; Galán, L; Guerrero-Sola, A; Benito-Martin, M S; Vela, A; Arranz-Tagarro, J A; García, A G

2014-01-01

The neurotoxic effects of cerebrospinal fluid (CSF) from patients with amyotrophic lateral sclerosis (ALS) have been reported by various authors who have attributed this neurotoxicity to the glutamate in CSF-ALS. Cultures of rat embryonic cortical neurons were exposed to CSF from ALS patients during an incubation period of 24 hours. Optical microscopy was used to compare cellular changes to those elicited by exposure to 100μm glutamate, and confocal microscopy was used to evaluate immunohistochemistry for caspase-3, TNFα, and peripherin. In the culture exposed to CSF-ALS, we observed cells with nuclear fragmentation and scarce or null structural modifications to the cytoplasmic organelles or to plasma membrane maintenance. This did not occur in the culture exposed to glutamate. The culture exposed to CSF-ALS also demonstrated increases in caspase-3, TNFα, and in peripherin co-locating with caspase-3, but not with TNFα, suggesting that TNFα may play an early role in the process of apoptosis. CFS-ALS cytotoxicity is not related to glutamate. It initially affects the nucleus without altering the cytoplasmic membrane. It causes cytoplasmic apoptosis that involves an increase in caspase-3 co-located with peripherin, which is also overexpressed. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

PubMed Central

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Investigating PID shunting in polycrystalline silicon modules via multiscale, multitechnique characterization

DOE PAGES

Harvey, Steven P.; Moseley, John; Norman, Andrew; ...

2018-02-27

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

New and improved ways to treat hydrocephalus: Pursuit of a smart shunt

PubMed Central

Lutz, Barry R.; Venkataraman, Pranav; Browd, Samuel R.

2013-01-01

The most common treatment for hydrocephalus is placement of a cerebrospinal fluid shunt to supplement or replace lost drainage capacity. Shunts are life-saving devices but are notorious for high failure rates, difficulty of diagnosing failure, and limited control options. Shunt designs have changed little since their introduction in 1950s, and the few changes introduced have had little to no impact on these long-standing problems. For decades, the community has envisioned a “smart shunt” that could provide advanced control, diagnostics, and communication based on implanted sensors, feedback control, and telemetry. The most emphasized contribution of smart shunts is the potential for advanced control algorithms, such as weaning from shunt dependency and personalized control. With sensor-based control comes the opportunity to provide data to the physician on patient condition and shunt function, perhaps even by a smart phone. An often ignored but highly valuable contribution would be designs that correct the high failure rates of existing shunts. Despite the long history and increasing development activity in the past decade, patients are yet to see a commercialized smart shunt. Most smart shunt development focuses on concepts or on isolated technical features, but successful smart shunt designs will be a balance between technical feasibility, economic viability, and acceptable regulatory risk. Here, we present the status of this effort and a framework for understanding the challenges and opportunities that will guide introduction of smart shunts into patient care. PMID:23653889

Hepatic vascular shunts: embryology and imaging appearances

PubMed Central

Bhargava, P; Vaidya, S; Kolokythas, O; Katz, D S; Dighe, M

2011-01-01

The purpose of this pictorial review is to understand the embryological basis of the development of congenital hepatic vascular shunts and to review the multimodality imaging appearances of congenital and acquired hepatic vascular shunts. Hepatic vascular shunts are commonly seen in imaging. Familiarity with their characteristic appearances is important in order to accurately characterise these shunts and diagnose the underlying disorders. PMID:22101582

Treatment of refractory chylothorax with externalized pleuroperitoneal shunts in children.

PubMed

Wolff, A B; Silen, M L; Kokoska, E R; Rodgers, B M

1999-09-01

Traditional therapy for refractory chylothorax in the pediatric population has included pleurodesis and thoracic duct ligation. These procedures are associated with high morbidity and questionable success rates. We retrospectively reviewed our experience with 15 patients who underwent treatment for chylous effusions using pleuroperitoneal shunts with exteriorized pump chambers. Mean patient age at time of shunt placement was 2.1 (0.1 to 11.5) years and the most common indication (7 of 15) was refractory chylothorax following surgical correction of congenital heart disease. Mean chylothorax duration before shunt placement was 76 (5 to 810) days and shunts were in place for an average of 104 (12 to 365) days. A total of 19 chylous effusions (pleural or pericardial) were treated with shunts. Nine of 11 right-sided chylothoraces, 5 of 6 left-sided chylothoraces, and 2 of 2 chylopericardia resolved with shunt therapy (84% total). Pleuroperitoneal shunting failed to clear the effusion in 3 children. There were six episodes of shunt malfunction that were repaired and two episodes of infection. Inguinal or umbilical hernia developed in 4 patients. Externalized pleuroperitoneal shunting is a safe, effective, and minimally invasive treatment for children with refractory chylous effusions.

Naegleria fowleri That Induces Primary Amoebic Meningoencephalitis: Rapid Diagnosis and Rare Case of Survival in a 12-Year-Old Caucasian Girl.

PubMed

Dunn, Andrew L; Reed, Tameika; Stewart, Charlotte; Levy, Rebecca A

2016-05-01

Primary amoebic meningoencephalitis (PAM) is a rare and almost always fatal disease that is caused by Naegleria fowleri, a freshwater thermophilic amoeba. Our case involves an adolescent female who presented with fever of unknown origin. A lumbar puncture was performed, and the Wright-Giemsa and Gram stained cerebrospinal fluid (CSF) cytospin slides showed numerous organisms. Experienced medical technologists in the microbiology and hematology laboratories identified the organisms as morphologically consistent with Naegleria species. The laboratory made a rapid diagnosis and alerted emergency department care providers within 75 minutes. The patient was treated for PAM with amphotericin, rifampin, azithromycin, fluconazole and aggressive supportive therapy including dexamethasone. The Centers for Disease Control and Prevention (CDC) was contacted, and miltefosine, an investigational medication, was started. Additional treatment included an intraventricular shunt and controlled hypothermia in order to mitigate potential cerebral edema. Our patient is a rare success story, as she was diagnosed swiftly, successfully treated, and survived PAM. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Management of the ventriculo-peritoneal shunt in pediatric patients during robot-assisted laparoscopic urologic procedures.

PubMed

Marchetti, Pablo; Razmaria, Aria; Zagaja, Greg P; Gundeti, Mohan S

2011-02-01

Infection or malfunction of ventriculo-peritoneal (VP) shunts is a severe complication during laparoscopic surgery involving the gastrointestinal or urinary tract. It has been recently suggested to externalize the shunt or convert into a ventriculo-atrial shunt to prevent this complication with laparoscopic approach. Herein, we present a novel technique for management of the VP shunt during robot-assisted laparoscopic (RAL) urologic procedures. After port placement and diagnostic peritoneoscopy, an Endopouch bag (Ethicon Endo-Surgery) was inserted into the peritoneal cavity and the distal end of the shunt was placed into the pouch. The Endopouch suture was synched around the shunt and the pouch was placed in the subhepatic space during the surgery. The intraperitoneal pressure was maintained at 12 mm Hg during the entire procedure. Metronidazole, gentamicin, and vancomycin were administered as prophylaxis. Following the completion of the surgery and profuse irrigation of the peritoneal cavity, the shunt was repositioned within the peritoneum. We evaluated perioperative shunt-related complications. We used this technique in four patients with VP shunt undergoing RAL cystoplasty and appendicovesicostomy and/or colonic enema channel formation. The average age of the patient at surgery was 10.8 (7-14) years. One patient was converted to open because of failure to progress due to multiple adhesions and the shunt was externalized temporarily. At a mean follow-up of 13 (3-20) months, no shunt-related complications were seen. In our preliminary experience, the use of an intracorporeal Endopouch bag with controlled pneumoperitoneal pressure to protect the VP shunt may be an effective alternative to prevent complications related to it during RAL urologic surgery involving the gastrointestinal or urinary tract. Further studies will be needed to confirm our results.

Endoscopic third ventriculostomy with/without choroid plexus cauterization for hydrocephalus due to hemorrhage, infection, Dandy-Walker malformation, and neural tube defect: a meta-analysis.

PubMed

Zandian, Anthony; Haffner, Matthew; Johnson, James; Rozzelle, Curtis J; Tubbs, R Shane; Loukas, Marios

2014-04-01

Endoscopic third ventriculostomy (ETV) is a viable alternative to CSF shunting in hydrocephalic patients and is used with varying degrees of success dependent on age and etiology. The purpose of this meta-analysis is to analyze data on ETV and ETV/CPC (choroid plexus cauterization) outcomes in hopes of providing a clear understanding of their limitations in patients with hydrocephalus due to hemorrhage, infection, Dandy-Walker malformation, or neural tube disorders. An extensive PubMed search dating back 11 years was performed on primary ETV or ETV/CPC procedures for hydrocephalus due to infection, hemorrhage, neural tube defects, and Dandy-Walker malformation. ETV success was defined as no intraoperative or post-operative complications and no need for revision surgery at follow-up. Ten studies were identified for analysis. The data represent 534 patients undergoing primary ETV and 167 patients undergoing primary ETV/CPC. The ETV group reached a 55 % success rate, while the ETV/CPC group reached a 67 % success rate. Success rates of ETV alone for hydrocephalus due to infection, neural tube defects, and intraventricular hemorrhage reached 54, 55, and 57 %, respectively. 84 % success was found in patients older than 2 years of age and 52 % success in patients less than 2 years of age. ETV is a valid treatment for hydrocephalus of any etiology. There exists a small difference in success rates between infection, hemorrhage, and neural tube disorders, though not enough to discount ETV for these etiologies. Initial data utilizing ETV/CPC are promising, and additional studies will need to be done to verify such results.

Causes and Timing of Unplanned Early Readmission After Neurosurgery.

PubMed

Taylor, Blake E S; Youngerman, Brett E; Goldstein, Hannah; Kabat, Daniel H; Appelboom, Geoffrey; Gold, William E; Connolly, Edward Sander

2016-09-01

Reducing the rate of 30-day hospital readmission has become a priority in healthcare quality improvement policy, with a focus on better characterizing the reasons for unplanned readmission. In neurosurgery, however, peer-reviewed analyses describing the patterns of readmission have been limited in their number and generalizability. To determine the incidence, timing, and causes of 30-day readmission after neurosurgical procedures. We conducted a retrospective longitudinal study from 2009 to 2012 using the Statewide Planning And Research Cooperative System, which collects patient-level details for all admissions and discharges within New York. We identified patients readmitted within 30 days of initial discharge. The rate of, reasons for, and time to readmission were determined overall and within 4 subgroups: craniotomies, cranial surgery without craniotomy, spine, and neuroendovascular procedures. There were 163 743 index admissions, of whom 14 791 (9.03%) were readmitted. The most common reasons for unplanned readmission were infection (29.52%) and medical complications (19.22%). Median time to readmission was 11 days, with hemorrhagic strokes and seizures occurring earlier, and medical complications and infections occurring later. Readmission rates were highest among patients undergoing cerebrospinal fluid shunt revision and malignant tumor resection (15.57%-22.60%). Spinal decompressions, however, accounted for the largest volume of readmissions (33.13%). Many readmissions may be preventable and occur at predictable time intervals. The causes and timing of readmission vary significantly across neurosurgical subgroups. Future studies should focus on detecting specific complications in select cohorts at predefined time points, which may allow for interventions to lower costs and reduce patient morbidity. CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System.

49 CFR 236.838 - Wire, shunt.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Wire, shunt. 236.838 Section 236.838 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Wire, shunt. A wire forming part of a shunt circuit. ...

49 CFR 236.838 - Wire, shunt.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Wire, shunt. 236.838 Section 236.838 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Wire, shunt. A wire forming part of a shunt circuit. ...

Shunt Intervention for Possible Idiopathic Normal Pressure Hydrocephalus Improves Patient Outcomes: A Nationwide Hospital-Based Survey in Japan.

PubMed

Nakajima, Madoka; Miyajima, Masakazu; Ogino, Ikuko; Akiba, Chihiro; Kawamura, Kaito; Kurosawa, Michiko; Kuriyama, Nagato; Watanabe, Yoshiyuki; Fukushima, Wakaba; Mori, Etsuro; Kato, Takeo; Sugano, Hidenori; Karagiozov, Kostadin; Arai, Hajime

2018-01-01

Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan. Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as "improved," while the remaining patients were classified as "non-improved." In the shunt intervention ( n = 437) and non-shunt intervention ( n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U -test. Finally, we examined subjects in the shunt intervention group ( n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt ( n = 540). Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31-0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) ( p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference. Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective.

Intracardiac Shunting and Stroke in Children: A Systematic Review

PubMed Central

Dowling, Michael M.; Ikemba, Catherine M.

2017-01-01

In adults, patent foramen ovale or other potential intracardiac shunts are established risk factors for stroke via paradoxical embolization. Stroke is less common in children and risk factors differ. The authors examined the literature on intracardiac shunting and stroke in children, identifying the methods employed, the prevalence of detectible intracardiac shunts, associated conditions, and treatments. PubMed searches with keywords related to intracardiac shunting and stroke in children identified articles of interest. Additional articles were identified via citations in these articles or in reviews. The authors found that studies of intracardiac shunting in children with stroke are limited. No controlled studies were identified. Detection methods vary and the prevalence of echocardiographically detectible intracardiac shunting appears lower than reported in adults and autopsy studies. Defining the role of intracardiac shunting in pediatric stroke will require controlled studies with unified detection methods in populations stratified by additional risk factors for paradoxical embolization. Optimal treatment is unclear. PMID:21212453

Asymptomatic Congenital Intrahepatic Portosystemic Shunt.

PubMed

Brown, Karen M; Hal, Hassan

2009-01-01

Congenital (spontaneous) intrahepatic portosystemic shunt is rare in the English literature. Most cases of portosystemic shunt occur after trauma, surgery, liver biopsy or as a result of chronic portal hypertension. Chronic shunting may result in encephalopathy, bleeding or hyperinsulinism. We report a case of an asymptomatic adult female with a presumed congenital intrahepatic portosystemic shunt and discuss the pertinent imaging findings and important key concepts related to this condition.

Occipitocervical fusion using a contoured rod and wire construct in children: a reappraisal of a vintage technique.

PubMed

Klimo, Paul; Astur, Nelson; Gabrick, Kyle; Warner, William C; Muhlbauer, Michael S

2013-02-01

Many methods to stabilize and fuse the craniocervical junction have been described. One of the early designs was a contoured (Luque) rod fixated with wires, the so-called Hartshill-Ransford loop. In this study, the authors report their 20-year experience with this surgical technique in children. The authors reviewed the medical records of patients 18 years of age or younger who underwent dorsal occipitocervical fusion procedures between March 1992 and March 2012 at Le Bonheur Children's Hospital using a contoured rod and wire construct. Data on basic patient characteristics, causes of instability, neurological function at presentation and at last follow-up, details of surgery, complications, and radiographic outcome were collected. Twenty patients (11 male) were identified, with a mean age of 5.5 years (range 1-18 years) and a median follow-up of 43.5 months. Fourteen patients had atlantooccipital dislocation, 2 patients had atlantoaxial fracture-dissociations, 2 had Down syndrome with occipitocervical and atlantoaxial instability, 1 had an epithelioid sarcoma from the clivus to C-2, and 1 had an anomalous atlas with resultant occipitocervical instability. Surgical stabilization extended from the occiput to C-1 in 3 patients, C-2 in 6, C-3 in 8, and to C-4 in 3. Bone morphogenetic protein was used in 2 patients. Two patients were placed in a halo orthosis; the rest were kept in a hard collar for 6-8 weeks. All patients were neurologically stable after surgery. One patient with a dural tear experienced wound dehiscence with CSF leakage and required reoperation. Eighteen patients went on to achieve fusion within 6 months of surgery; 1 patient was initially lost to follow-up, but recent imaging demonstrated a solid fusion. There were no early hardware or bone failures requiring hardware removal, but radiographs obtained 8 years after surgery showed that 1 patient had an asymptomatic fractured rod. There were no instances of symptomatic junctional degeneration, and no patient was found to have increasing lordosis over the fused segments. Five (31%) of the 16 trauma patients required a shunt for hydrocephalus. Despite the proliferation of screw-fixation techniques for craniocervical instability in children, the contoured rod-wire construct remains an effective, less expensive, and technically easier alternative that has been in use for almost 30 years. It confers immediate stability, and therefore most patients will not need to be placed in a halo device postoperatively. A secondary observation in our series was the high (30%) rate of hydrocephalus requiring a shunt in patients with traumatic instability.

Validated linear dynamic model of electrically-shunted magnetostrictive transducers with application to structural vibration control

NASA Astrophysics Data System (ADS)

Scheidler, Justin J.; Asnani, Vivake M.

2017-03-01

This paper presents a linear model of the fully-coupled electromechanical behavior of a generally-shunted magnetostrictive transducer. The impedance and admittance representations of the model are reported. The model is used to derive the effect of the shunt’s electrical impedance on the storage modulus and loss factor of the transducer without neglecting the inherent resistance of the transducer’s coil. The expressions are normalized and then shown to also represent generally-shunted piezoelectric materials that have a finite leakage resistance. The generalized expressions are simplified for three shunts: resistive, series resistive-capacitive, and inductive, which are considered for shunt damping, resonant shunt damping, and stiffness tuning, respectively. For each shunt, the storage modulus and loss factor are plotted for a wide range of the normalized parameters. Then, important trends and their impact on different applications are discussed. An experimental validation of the transducer model is presented for the case of resistive and resonant shunts. The model closely predicts the measured response for a variety of operating conditions. This paper also introduces a model for the dynamic compliance of a vibrating structure that is coupled to a magnetostrictive transducer for shunt damping and resonant shunt damping applications. This compliance is normalized and then shown to be analogous to that of a structure that is coupled to a piezoelectric material. The derived analogies allow for the observations and equations in the existing literature on structural vibration control using shunted piezoelectric materials to be directly applied to the case of shunted magnetostrictive transducers.

Internal carotid artery rupture caused by carotid shunt insertion.

PubMed

Illuminati, Giulio; Caliò, Francesco G; Pizzardi, Giulia; Vietri, Francesco

2015-01-01

Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-resonant electromagnetic shunt in base isolation for vibration damping and energy harvesting

NASA Astrophysics Data System (ADS)

Pei, Yalu; Liu, Yilun; Zuo, Lei

2018-06-01

This paper investigates multi-resonant electromagnetic shunts applied to base isolation for dual-function vibration damping and energy harvesting. Two multi-mode shunt circuit configurations, namely parallel and series, are proposed and optimized based on the H2 criteria. The root-mean-square (RMS) value of the relative displacement between the base and the primary structure is minimized. Practically, this will improve the safety of base-isolated buildings subjected the broad bandwidth ground acceleration. Case studies of a base-isolated building are conducted in both the frequency and time domains to investigate the effectiveness of multi-resonant electromagnetic shunts under recorded earthquake signals. It shows that both multi-mode shunt circuits outperform traditional single mode shunt circuits by suppressing the first and the second vibration modes simultaneously. Moreover, for the same stiffness ratio, the parallel shunt circuit is more effective at harvesting energy and suppressing vibration, and can more robustly handle parameter mistuning than the series shunt circuit. Furthermore, this paper discusses experimental validation of the effectiveness of multi-resonant electromagnetic shunts for vibration damping and energy harvesting on a scaled-down base isolation system.

Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: Case Report and Review of Literature.

PubMed

Yoneoka, Yuichiro; Akiyama, Katsuhiko; Seki, Yasuhiro; Hasegawa, Go; Kakita, Akiyoshi

2018-03-01

Frontoethmoidal schwannomas are rare. No case manifesting exertional cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our knowledge. In this report, we describe an extremely rare case of frontoethmoidal schwannoma extending through the olfactory groove with exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was presented to our clinic for frequent nasal discharge on exertion. A postcontrast computed tomographic scan demonstrated heterogeneously enhanced tumor from the anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1-weighted magnetic resonance image revealed a well-defined heterogeneously enhanced tumor situated in the midline anterior cranial fossa and anterior ethmoid sinus. After the resection, the defect of the right anterior skull base was reconstructed with a fascia graft and adipose tissue taken from the abdomen, as well as a pedicle periosteum flap. A histologic examination revealed the tumor as schwannoma. Her rhinorrhea completely resolved. She regained her sense of smell and taste 1 month after the operation. According to previous reports, olfactory groove, and paraolfactory groove/periolfactory groove schwannomas can be divided into 4 types: subfrontal, nasoethmoidal, frontoethmoidal, and ethmofrontal. Among them, a frontoethmoidal schwannoma can manifest exertional CSF rhinorrhea as an initial symptom. Copyright © 2018 Elsevier Inc. All rights reserved.

Ehrlichia Meningitis Mimicking Aneurysmal Subarachnoid Hemorrhage: A Case Study for Medical Decision-Making Heuristics.

PubMed

Dredla, Brynn; Freeman, William D

2016-04-01

Thunderclap headache is a sudden and severe headache that can occur after an aneurysmal subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage is a medical emergency that requires prompt attention and hospitalization. Patients with thunderclap headache often undergo a noncontrast head computed tomography (CT) scan to ascertain SAH bleeding and, if the scan is negative, then undergo a lumbar puncture to look for cerebrospinal fluid (CSF) red blood cells (RBCs), which would be consistent with an aneurysmal leak. If the initial CT is negative and CSF is positive for RBCs, patients are usually admitted to the hospital for evaluation of intracranial aneurysm. We encountered a patient with thunderclap headache whose initial head CT was negative for SAH and whose CSF tested positive for RBCs. The patient was referred to our center for evaluation and management of aneurysmal SAH. However, on careful review of the patient's medical history, serum laboratory values, and spinal fluid values, the patient was diagnosed with Ehrlichia chaffeensis meningitis. While Ehrlichia meningitis is rare, it is important to recognize the clinical clues that could help avoid formal cerebral angiography, a costly and potentially unnecessary procedure. We present how this case represented a cognitive framing bias and anchoring heuristic as well as steps that medical providers can use to prevent such cognitive errors in diagnosis.

[Clinical experience with the Sp[hy adjustable valve in the treatment of adult hydrocephalus. A series of 147 cases].

PubMed

Bret, P; Guyotat, J; Ricci, A C; Mottolese, C; Jouanneau, E

1999-05-01

Evaluate the advantages, results and drawbacks of the Sophy adjustable valve (SV) in the treatment of hydrocephalus in the adult. One-hundred and forty-seven adult hydrocephalic patients (mean age = 64.5 years) shunted with a SV between 1990 and 1997 were retrospectively reviewed. Etiologies of hydrocephalus were: "normal pressure" chronic hydrocephalus (NPH) in 124 and tumoral hydrocephalus with intracranial hypertension in 23 patients. One-hundred fifty shunts were established in 147 patients: 14 ventriculoatrial and 136 ventriculoperitoneal shunts. The initial pressure settings of the SV were: high pressure: 12 times (8%), medium pressure: 136 times (90.6%) and low pressure: 2 times (1.3%). Sixteen patients were lost to follow-up. Two patients died within hours following the procedure. So, the results were analyzed in the 129 remaining patients, with a follow-up of 16.7 months (+/- 17.8). Three patients died from shunted-related causes (2.3%). Eighty-four patients had good results (65%), 25 had fair results (19.5%) and 20 failed to improve or deteriorated (15.5%) after shunting. Fifty-three reoperations were performed in 44 patients (34%), including 37 procedures for mechanical obstruction and 6 for septic complications. Subdural effusions (SDE) occurred in 16 patients (12.5%): 10 surgical evacuations were required in 7 patients; 8 patients were successfully treated using uprating of the SV pressure alone; one was managed conservatively. Fifty-eight pressure readjustments were performed in 47 patients. The pressure settings were uprated 28 times in patients showing clinical or computerized tomographic (CT) features suggesting overdrainage; 20 of those proved to be successful (71.5%). The pressure settings were lowered 30 times in patients showing a lack of improvement after shunting, attributed to underdrainage; only 12 of those proved to be successful (40%). Spontaneous changes of the pressure settings were observed in 14 patients (10.8%). After a MRI exposure, SV pressure changes were observed in 64% of patients. The technological refinements that have been proposed to eliminate the overdrainage which occurs in most usual cerebrospinal fluid shunts are reviewed. The SV valve has allowed non-invasive adjustments of its opening pressure in patients showing complications ascribed to inappropriate drainage. The need for additional surgery was eliminated in 20% to 25% of patients of the present series. Because of frequent spontaneous and magnetic resonance-induced pressure changes, the need for repeated controls of valve pressure is to be reemphasized. This experience suggests that the SV represents a substantial improvement over standard fixed-pressure valves.

Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

2002-11-01

Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P < or = 0.0001) increased WBC counts, CFC frequencies, and CFC absolute numbers by 2-, 13-, and 27-fold, respectively. As compared with control mice, the combined administration of Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P < or = 0.0001) increased WBC counts, frequencies and absolute numbers of CFCs by 4-, 38-, and 119-fold, respectively. As compared with rhG-CSF alone, administration of Defibrotide plus rhG-CSF resulted in a significant increase (P < or = 0.001) of the frequency of circulating long-term culture-initiating cells. In addition, transplantation of 2 x 10(5) rhG-CSF- or Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P < or = 0.001), suggesting that the mobilizing effect of Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

Treatment of extrahepatic portal hypertension following a whipple procedure with a Rex shunt: report of a case.

PubMed

Reichman, Trevor W; Anthony, Tiffany; Testa, Giuliano

2011-02-01

The Rex shunt is a mesenteric vein to left portal vein decompressive shunt used for the treatment of portal vein thrombosis and portal hypertension. Its use has been reported primarily in the pediatric population where portal vein thrombosis occurs with some frequency. The shunt is thought to represent a more physiologic shunt, since it restores hepatopedal blood flow through the liver. This report describes the use of this shunt in an adult who had frequent gastrointestinal bleeding secondary to extrahepatic portal vein thrombosis, which occurred as a complication after a pancreaticoduodenectomy.

Evaluation of in vivo behavior of ameroid ring constrictors in dogs with congenital extrahepatic portosystemic shunts using computed tomography.

PubMed

Hunt, Geraldine B; Culp, William T N; Mayhew, Kelli N; Mayhew, Philipp; Steffey, Michele A; Zwingenberger, Allison

2014-10-01

To evaluate the in vivo pattern of ameroid constrictor closure of congenital extrahepatic portosystemic shunts in dogs. Prospective study. Dogs (n = 22) with congenital extrahepatic portosystemic shunts. Contrast-enhanced computed tomography was performed immediately before, and at least 8 weeks after placement of ameroid ring constrictors. Plastic-encased ameroid constrictors were used in 17 dogs and metal constrictors in 5 dogs. Presence of residual flow through the portosystemic shunt, additional anomalous vessels, acquired shunts and soft tissue associated with the ameroid constrictor was recorded. Postoperative internal diameter was recorded for the 17 plastic constrictors. Correlations between internal diameter and pre- and postoperative serum protein concentration were analyzed. No ameroid constrictor closed completely: shunt occlusion was always dependent on soft tissue within the ameroid ring. Residual flow through the shunt was present in 4 dogs (18%), although this caused persistent elevation of shunt fraction in only 1 dog (dog 8). The change in ameroid constrictor internal diameter was not significantly correlated with serum protein concentration. Complete shunt occlusion after AC placement is usually dependent on soft tissue reaction. Ameroid constrictors ≥5 mm diameter may not promote complete shunt occlusion. © Copyright 2014 by The American College of Veterinary Surgeons.

Serum hyaluronic acid in dogs with congenital portosystemic shunts.

PubMed

Seki, M; Asano, K; Sakai, M; Kanno, N; Teshima, K; Edamura, K; Tanaka, S

2010-05-01

To compare the serum level of hyaluronic acid in dogs with congenital portosystemic shunt with that in healthy dogs and to investigate the perioperative change in serum hyaluronic acid following shunt attenuation. Blood samples were obtained from 29 congenital portosystemic shunt dogs before the operation, and 2 and 4 weeks after the operation from 17 and 7 dogs, respectively. The serum hyaluronic acid level of these dogs was measured and compared with that of 10 healthy beagles. The median preoperative hyaluronic acid level in dogs with congenital portosystemic shunt was significantly elevated compared with that in healthy dogs. Furthermore, the median postoperative hyaluronic acid level significantly decreased compared with the median preoperative levels in congenital portosystemic shunt dogs. In the case of dogs with congenital portosystemic shunt, the reduction of intrahepatic portal blood flow might lower the clearance rate of hyaluronic acid in hepatic sinusoidal endothelial cells, so hyaluronic acid clearance could be improved by attenuation of a shunt vessel. Hence, serum hyaluronic acid levels might be useful to evaluate liver function and also have the potential to evaluate successful attenuation of a shunt vessel in dogs with congenital portosystemic shunt. Further investigations are required to clarify whether serum hyaluronic acid offers significant benefits over existing markers such as serum bile acid or ammonia concentrations.

Effect of bladder augmentation on VP shunt failure rates in spina bifida.

PubMed

Gonzalez, Dani O; Cooper, Jennifer N; McLeod, Daryl J

2017-12-11

Most patients with spina bifida require ventriculoperitoneal (VP) shunt placement. Some also require bladder augmentation, which may increase the risk of VP shunt malfunction and/or failure. The aim of this study was to assess whether bladder augmentation affects the rate of VP shunt failure in this population. Using the Pediatric Health Information System, we studied patients with spina bifida born between 1992 and 2014 who underwent VP shunt placement. Using conditional logistic regression, we compared age- and hospital-matched patients who did and did not undergo a bladder augmentation to determine their difference in rates of VP shunt failure. There were 4192 patients with spina bifida who underwent both surgical closure and VP shunt placement. Of these, 203 patients with bladder augmentation could be matched to 593 patients without bladder augmentation. VP shunt failure occurred within 2 years in 7.7% of patients, the majority of whom were in the group who underwent bladder augmentation (87%). After adjusting for confounders, undergoing bladder augmentation was independently associated with VP shunt failure (HR: 33.5, 95% CI: 13.15-85.44, p< 0.001). Bladder augmentation appears to be associated with VP shunt failure. Additional studies are necessary to better define this relationship and identify risk-reduction techniques.

Conversion of Low-Flow Priapism to High-Flow State Using T-Shunt with Tunneling.

PubMed

Mistry, Neil A; Tadros, Nicholas N; Hedges, Jason C

2017-01-01

Introduction . The three types of priapism are stuttering, arterial (high-flow, nonischemic), and venoocclusive (low-flow, ischemic). These are usually distinct entities and rarely occur in the same patient. T-shunts and other distal shunts are frequently combined with tunneling, but a seldom recognized potential complication is conversion to a high-flow state. Case Presentation . We describe 2 cases of men who presented with low-flow priapism episodes that were treated using T-shunts with tunneling that resulted with both men having recurrent erections shortly after surgery that were found to be consistent with high-flow states. Case 1 was a 33-year-old male with sickle cell anemia and case 2 was a 24-year-old male with idiopathic thrombocytopenic purpura. In both cases the men were observed over several weeks and both men returned to normal erectile function. Conclusions . Historically, proximal shunts were performed only in cases when distal shunts failed and carry a higher risk of serious complications. T-shunts and other distal shunts combined with tunneling are being used more frequently in place of proximal shunts. These cases illustrate how postoperative erections after T-shunts with tunneling can signify a conversion from low-flow to high-flow states and could potentially be misdiagnosed as an operative failure.

Flutamide and biomarkers in women at high risk for ovarian cancer: preclinical and clinical evidence.

PubMed

Gruessner, Christine; Gruessner, Angelika; Glaser, Katherine; AbuShahin, Nisreen; Zhou, Yi; Laughren, Cynthia; Wright, Heather; Pinkerton, Samantha; Yi, Xiaofang; Stoffer, Jha'nae; Azodi, Masoud; Zheng, Wenxin; Chambers, Setsuko K

2014-09-01

We hypothesized that (i) preclinical biologic evidence exists for the role of androgens in ovarian cancer development and (ii) flutamide treatment of women at high risk for ovarian cancer may identify meaningful tissue biomarkers of androgen action and of ovarian cancer initiation. We showed that androgen ablation of male mice led to a 24-fold decrease in tumor burden from serous ovarian cells. In a phase II study, we studied the effect of preoperative flutamide treatment (125 mg/day × 6 weeks) in 12 women versus 47 controls, 47% with BRCA mutation. We analyzed immunohistochemical scores of candidate proteins CSF-1, CSF-1R, and ErbB4 in the epithelium and stroma of fallopian tube, ovary, and ovarian endosalpingiosis. Flutamide decreased the levels, notably, of CSF-1 and ErbB4 in ovarian stroma (P ≤ 0.0006) and ovarian endosalpingiosis (P ≤ 0.01), ErbB4 in ovarian epithelium (P = 0.006), and CSF-1R in ovarian endosalpingiosis (P = 0.009). Our logistic regression model clearly distinguished the flutamide patients from controls (P ≤ 0.0001). Our analysis of the precision of this model of CSF-1 and ErbB4 expression in ovarian stroma achieved 100% sensitivity and 97% specificity (AUC = 0.99). Thus, our data suggest that a short 6-week exposure of flutamide reversed elevated levels of CSF-1 and ErbB4 (both of which we had previously found correlated with high risk status). CSF-1 and ErbB4 in ovarian stroma led to a model with high predictive value for flutamide sensitivity. The effect of flutamide on marker expression in ovarian endosalpingiosis, previously associated with BRCA carrier status, suggests that ovarian endosalpingiosis may be a latent precursor to pelvic serous cancers. ©2014 American Association for Cancer Research.

A Hospital Based Study on Estimation of Adenosine Deaminase Activity (ADA) in Cerebrospinal Fluid (CSF) in Various Types of Meningitis.

PubMed

Agarwal, Ashok Kumar; Bansal, Sonia; Nand, Vidya

2014-02-01

Tuberculosis kills 3.70 lakh patients in India every year,out of which 7-12 % are meningeal involvement. Delay in its diagnosis and initiation of treatment results in poor prognosis and squeal in up to 25% of cases. The aim of the present study is to look for a simple, rapid, cost effective, and fairly specific test in differentiating tubercular aetiology from other causes of meningitis. In the present study we measured the adenosine deaminase activity (ADA) in Cerebrospinal Fluid (CSF) of Tubercular Meningitis (TBM) and non-TBM patients. Fifty six patients attending hospital with symptoms and signs of meningitis were selected and divided into three groups: tubercular, pyogenic, and aseptic meningitis, depending upon the accepted criteria. CSF was drawn and ADA estimated. Out of 32 tubercular patients, 28 had CSF-ADA at or above the cut-off value while four had below. Out of 24 non-tuberculous patients (pyogenic and aseptic meningitis), two aseptic meningitis (AM) patient had ADA levels at or above the cut-off value while 22 had below this value. RESULTS of our study indicate that ADA level estimation in CSF is not only of considerable value in the diagnosis of TBM, CSF, and ADA level 10 U/L as a cut-off value with sensitivity 87.5% and specificity 83.33% and positive predictive value of the test was 87.5%.and 83.3% negative predictive value. It can be concluded that ADA estimation in CSF is not only simple, inexpensive and rapid but also fairly specific method for making a diagnosis of tuberculous aetiology in TBM, especially when there is a dilemma of differentiating the tuberculous aetiology from non-tuberculous ones. For this reason ADA estimation in TBM may find a place as a routine investigation.

Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

PubMed Central

Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use. PMID:24523921

The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer.

PubMed

Wang, Peng; Piao, Yingzhe; Zhang, Xiaohui; Li, Wenliang; Hao, Xishan

2013-01-01

We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 μg/L, NSE > 14.6 μg/L and CYFRA21-1 > 5.5 μg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of MC.

Complications of congenital portosystemic shunts in children: therapeutic options and outcomes.

PubMed

Franchi-Abella, Stéphanie; Branchereau, Sophie; Lambert, Virginie; Fabre, Monique; Steimberg, Clarisa; Losay, Jean; Riou, Jean-Yves; Pariente, Danièle; Gauthier, Frédéric; Jacquemin, Emmanuel; Bernard, Olivier

2010-09-01

Congenital portosystemic shunts are rare vascular malformations that lead to severe complications. Their management is controversial. The aim of this study was to propose a clear definition of the risks and management of congenital portosystemic shunts in children according to our experience and a review of the literature. Twenty-two children with a complicated congenital portosystemic shunt were studied in our institution. When necessary, management included portal pressure measurement and portal vein angiography during an occlusion test and closure of the shunt by surgical and/or endovascular methods. Five neonates with intrahepatic shunts presented with cholestasis that resolved spontaneously, and 17 older children presented with liver tumors (13) and/or hepatopulmonary syndrome (2), pulmonary artery hypertension (3), portosystemic encephalopathy (3), heart failure (1), and glomerulonephritis (1). The portosystemic shunt was extrahepatic (11) or intrahepatic (6). Portosystemic shunts were closed by endovascular methods in 5 children and surgically in 10, 4 of whom had portal pressure during occlusion above 35 mmHg and extremely hypoplastic or undetectable portal veins requiring banding of the fistula before closure. Shunt closure resulted in restoration of intrahepatic portal flow in all, with complete or partial regression of benign liver masses, and regression or stabilization of pulmonary, cardiac, neurological, and renal complications. Congenital portosystemic shunt carries risks of severe complications in children. Closure of a shunt persisting after age 2 years should be considered preventively. Intrahepatic portal flux restoration can be expected, even when intrahepatic portal veins are extremely hypoplastic or undetectable.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harvey, Steven P.; Moseley, John; Norman, Andrew

We investigated the potential-induced degradation (PID) shunting mechanism in multicrystalline-silicon photovoltaic modules by using a multiscale, multitechnique characterization approach. Both field-stressed modules and laboratory-stressed mini modules were studied. We used photoluminescence, electroluminescence, and dark lock-in thermography imaging to identify degraded areas at the module scale. Small samples were then removed from degraded areas, laser marked, and imaged by scanning electron microscopy. We used simultaneous electron-beam induced current imaging and focused ion beam milling to mark around PID shunts for chemical analysis by time-of-flight secondary-ion mass spectrometry or to isolate individual shunt defects for transmission electron microscopy and atom-probe tomography analysis.more » By spanning a range of 10 orders of magnitude in size, this approach enabled us to investigate the root-cause mechanisms for PID shunting. We observed a direct correlation between recombination active shunts and sodium content. The sodium content in shunted areas peaks at the SiNX/Si interface and is consistently observed at a concentration of 0.1% to 2% in shunted areas. Analysis of samples subjected to PID recovery, either activated by electron beam or thermal effects only, reveals that recovery of isolated shunts correlates with diffusion of sodium out of the structural defects to the silicon surface. We observed the role of oxygen and chlorine in PID shunting and found that those species - although sometimes present in structural defects where PID shunting was observed - do not play a consistent role in PID shunting.« less

49 CFR 236.725 - Circuit, switch shunting.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Circuit, switch shunting. 236.725 Section 236.725 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Circuit, switch shunting. A shunting circuit which is closed through contacts of a switch circuit...

49 CFR 236.725 - Circuit, switch shunting.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Circuit, switch shunting. 236.725 Section 236.725 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Circuit, switch shunting. A shunting circuit which is closed through contacts of a switch circuit...